3-125037745-C-T

Variant names:

• chr3-125037745-C-T
• rs4679257
• NM_020733.2:c.317-8257G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020733.2(HEG1):​c.317-8257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,298 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.068 (523 hom., cov: 33)
• Consequence: HEG1 NM_020733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 1 publications found

Genes affected

HEG1 (HGNC:29227): (heart development protein with EGF like domains 1) Predicted to enable calcium ion binding activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of Rho-dependent protein serine/threonine kinase activity; and negative regulation of membrane permeability. Located in cell-cell junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEG1	NM_020733.2	c.317-8257G>A		intron_variant	Intron 1 of 16	ENST00000311127.9	NP_065784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEG1	ENST00000311127.9	c.317-8257G>A		intron_variant	Intron 1 of 16	5	NM_020733.2	ENSP00000311502.3
HEG1	ENST00000650592.2	c.317-8257G>A		intron_variant	Intron 1 of 17			ENSP00000515478.1

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10360 AN: 152180 Hom.: 523 Cov.: 33

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0536

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0680 AC: 10358 AN: 152298 Hom.: 523 Cov.: 33 AF XY: 0.0657 AC XY: 4890 AN XY: 74464

African (AFR) AF: 0.0173 AC: 721 AN: 41560

American (AMR) AF: 0.0477 AC: 730 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4830

European-Finnish (FIN) AF: 0.119 AC: 1261 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7152 AN: 68016

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0830 Hom.: 649

Bravo AF: 0.0625

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4679257; hg19: chr3-124756589;