ENST00000776537.1:n.-249T>C

Variant names:

• chr17-34252769-A-G
• rs1024611
• ENST00000776537.1:n.-249T>C

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000776537.1(ENSG00000301139):n.-249T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. Note: ENST00000776537.1 is not a MANE Select or MANE Plus Clinical transcript for ENSG00000301139; 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 0.287 (AC=43,619) in the gnomAD database across 152,162 control chromosomes, including 6,922 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.539. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Uncertain Significance (★).

• Frequency: Genomes: 𝑓 0.29 (6922 hom., cov: 33)
• Consequence: ENSG00000301139 ENST00000776537.1 upstream_gene
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:2
• Conservation: PhyloP100: -0.103
• Publications: 87 publications found

Genes affected

ENSG00000301139 (HGNC:):

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5392 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000776537.1. 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
	ENSG00000301139 ENST00000776537.1		n.-249T>C	upstream_gene	N/A	Prot:
	ENSG00000301139 ENST00000776538.1		n.-249T>C	upstream_gene	N/A	Prot:

ENSG00000301139 ENST00000776537.1

HGVSc / HGVSpn.-249T>C

Exon rankN/A

upstream_gene

Prot:

ENSG00000301139 ENST00000776538.1

HGVSc / HGVSpn.-249T>C

Exon rankN/A

upstream_gene

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 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.287	AC:43582	Hom:6908	AN:152044	Cov:33
GnomAD4 genome	AF: 0.287	AC:43619	Hom:6922	AN:152162	Cov:33
TOPMed (Bravo)	AF: 0.290	AC:76670	Hom:12496	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.279	AC:143748	Hom:21089	AN:514420	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.312	AC:730	Hom:112	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.573	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.370	AC:111	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.439	AC:1527	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.616	AC:4455	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.324	AC:57	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.663	AC:81432	Hom:26991	AN:122802	Cov:
Turkish Variome	AF: 0.291	AC:450	Hom:73	AN:1546	Cov:
UK10K	AF: 0.283	AC:2143	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.556	AC:4981	Hom:1377	AN:8960	Cov:

Showing 14 sources

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	1	CCL2-related disorder (2)
-	-	1	Spina bifida, susceptibility to (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.2
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.46
GPN-Star LLR	N/A	0.16
GPN-Star score	N/A	-0.16
PhyloP100	Benign	-0.10

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: rs1024611;

hg19: chr17-32579788;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar