rs4395444

Variant names:

• chr3-125008903-A-G
• rs4395444
• NM_020733.2:c.3193+802T>C

Variant summary

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

The NM_020733.2(HEG1):​c.3193+802T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,122 control chromosomes in the GnomAD database, including 27,915 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 0.60 (27915 hom., cov: 34)
• Consequence: HEG1 NM_020733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEG1	NM_020733.2	c.3193+802T>C		intron_variant	Intron 8 of 16	ENST00000311127.9	NP_065784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEG1	ENST00000311127.9	c.3193+802T>C		intron_variant	Intron 8 of 16	5	NM_020733.2	ENSP00000311502.3
HEG1	ENST00000650592.2	c.3493+802T>C		intron_variant	Intron 9 of 17			ENSP00000515478.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91870 AN: 152004 Hom.: 27905 Cov.: 34

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.604 AC: 91932 AN: 152122 Hom.: 27915 Cov.: 34 AF XY: 0.604 AC XY: 44948 AN XY: 74356

African (AFR) AF: 0.542 AC: 22482 AN: 41468

American (AMR) AF: 0.650 AC: 9944 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2411 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2923 AN: 5182

South Asian (SAS) AF: 0.651 AC: 3143 AN: 4826

European-Finnish (FIN) AF: 0.622 AC: 6552 AN: 10538

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42356 AN: 68018

Other (OTH) AF: 0.624 AC: 1320 AN: 2116

Alfa AF: 0.617 Hom.: 8558

Bravo AF: 0.604

Asia WGS AF: 0.612 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-0.41
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: rs4395444; hg19: chr3-124727747;