NM_203407.3:c.1272G>A (p.Gln424=) is a synonymous variant in EZHIP exon 1. SpliceAI predicts no splicing impact (max delta=0.02), consistent with a silent substitution.1 This variant is present in gnomAD v2.1 with a grpmax filtering allele frequency of 0.47% (82/204,972 alleles, 1 homozygote) and an East Asian subpopulation frequency of 0.54% (80/14,835 alleles, 1 homozygote), exceeding the 0.3% threshold expected for a rare disease variant and supporting a benign interpretation.2 The variant is absent from ClinVar and has not been reported in the published literature. No functional studies, segregation data, or case-control evidence exists to support pathogenicity.3 No pathogenic criteria are met. Benign evidence includes BS1 (supporting benign; population frequency), BP4 (supporting benign; in silico predictions), and BP7 (supporting benign; synonymous with silent splice prediction). Overall, the variant is classified as Likely Benign.4
EZHIP
Final classification
Likely Benign
EZHIP c.1272G>A · p.Gln424=
EZHIP
NM_203407.3:c.1272G>A (p.Gln424=) is a synonymous variant in EZHIP exon 1. SpliceAI predicts no splicing impact (max delta=0.02), consistent with a silent substitution.
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 supporting benign, BP4 supporting benign, BP7 supporting benign; combination = 3 supporting benign, which maps to Likely Benign.
Classification rationale
BS1BP4BP7
Likely Benign
EZHIP c.1272G>A
BS1 + BP4 + BP7
→
Likely Benign
Gene diagram
· NM_203407.3 · variants mapped to exon structure
EZHIP
NM_203407.3
Fetching transcript structure from UCSC…
Applied criteria · 3 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency · supports benign
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 0.000142255; MAF= 0.01423%, 81/569401 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00234497; MAF= 0.23450%, 72/30704 alleles, homozygotes = 1); grpmax FAF= 0.00190909.
v2.1
This variant is present in gnomAD v2.1 (AF= 0.000400055; MAF= 0.04001%, 82/204972 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00539265; MAF= 0.53927%, 80/14835 alleles, homozygotes = 1); grpmax FAF= 0.00468821.
🇨🇦 CA
This variant is present in gnomAD-Canada v1.0 (AF= 0.000414651002073255, 6/14470 alleles, homozygotes = 0).
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.014%
· 81 / 569,401
1 hom · FAF 0.19%
1 hom · FAF 0.19%
East Asian 72 / 30,704 |
0.23% 1 hom |
Remaining individuals 7 / 26,445 |
0.026% |
South Asian 1 / 44,788 |
0.0022% |
Admixed American 1 / 45,068 |
0.0022% |
+ 6 not observed (European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish))
gnomAD v2.1
0.04%
· 82 / 204,972
1 hom · FAF 0.47%
1 hom · FAF 0.47%
East Asian 80 / 14,835 |
0.54% 1 hom |
Remaining individuals 1 / 5,334 |
0.019% |
South Asian 1 / 19,053 |
0.0052% |
+ 5 not observed (African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish))
gnomAD Canada 🇨🇦
0.041%
· 6 / 14,470
0 hom · FAF 0.25%
0 hom · FAF 0.25%
East Asian 6 / 1,040 |
0.58% |
+ 8 not observed (African/African American, Latino/Admixed American, Ashkenazi Jewish, European (Finnish), Middle Eastern, European (non-Finnish), Remaining individuals, South Asian)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
Functional
Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Hotspots
This variant does not lie in a statistically significant hotspot.
Sources & reference links