chr4-105140377-C-A

Variant names:

• chr4-105140377-C-A
• rs7679673
• XM_047416559.1:c.*779-2659G>T

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The ENST00000504082.1(ENSG00000251259):n.110+133G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000504082.1 is not a MANE Select or MANE Plus Clinical transcript for ENSG00000251259; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.507 (AC=77,071) in the gnomAD database across 152,018 control chromosomes, including 20,408 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.781. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20408 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000251259 ENST00000504082.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 141 publications found

Genes affected

LOC124900868 (HGNC:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.781 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000504082.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ENSG00000251259 ENST00000504082.1	TSL:4	n.110+133G>T	intron	Intron 1 of 1	Prot:
	ENSG00000251259 ENST00000776606.1		n.149-2659G>T	intron	Intron 1 of 1	Prot:
	ENSG00000251259 ENST00000776607.1		n.371-2659G>T	intron	Intron 2 of 2	Prot:

ENSG00000251259 ENST00000504082.1

TSL:4

HGVSc / HGVSpn.110+133G>T

Exon rankIntron 1 of 1

intron

Prot:

ENSG00000251259 ENST00000776606.1

HGVSc / HGVSpn.149-2659G>T

Exon rankIntron 1 of 1

intron

Prot:

ENSG00000251259 ENST00000776607.1

HGVSc / HGVSpn.371-2659G>T

Exon rankIntron 2 of 2

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.507	AC:76970	Hom:20369	AN:151900	Cov:32
GnomAD4 exome Warning	AF:	AC:0	Hom:0	AN:0	Cov:
GnomAD4 genome	AF: 0.507	AC:77071	Hom:20408	AN:152018	Cov:32
TOPMed (Bravo)	AF: 0.510	AC:135119	Hom:36030	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.441	AC:237000	Hom:54414	AN:537562	Cov:
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.483	AC:1132	Hom:297	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.803	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.340	AC:102	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.681	AC:2361	Hom:	AN:3476	Cov:
Korea4K (4,157 Koreans)	AF: 0.811	AC:5863	Hom:	AN:7226	Cov:
Qatari Genome	AF: 0.551	AC:97	Hom:	AN:176	Cov:
Turkish Variome	AF: 0.523	AC:809	Hom:212	AN:1546	Cov:
UK10K	AF: 0.375	AC:2835	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.807	AC:7230	Hom:2924	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	2.1
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.82
DANN	Benign	0.30
GPN-Star LLR	N/A	5.8
GPN-Star score	N/A	1.3
PhyloP100	Benign	0.035

Showing 7 of 7 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs7679673;

hg19: chr4-106061534;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar