rs2228674

Variant names:

• chr3-125051238-A-G
• rs2228674
• NM_020733.2:c.316+4337T>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.316+4337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,224 control chromosomes in the GnomAD database, including 2,164 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 0.15 (2164 hom., cov: 32)
• Consequence: HEG1 NM_020733.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEG1	NM_020733.2	c.316+4337T>C		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.316+4337T>C		intron_variant	Intron 1 of 16	5	NM_020733.2	ENSP00000311502.3
HEG1	ENST00000650592.2	c.316+4337T>C		intron_variant	Intron 1 of 17			ENSP00000515478.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22166 AN: 152106 Hom.: 2163 Cov.: 32

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.146 AC: 22166 AN: 152224 Hom.: 2164 Cov.: 32 AF XY: 0.146 AC XY: 10881 AN XY: 74404

African (AFR) AF: 0.0368 AC: 1530 AN: 41558

American (AMR) AF: 0.138 AC: 2112 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3466

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5194

South Asian (SAS) AF: 0.144 AC: 693 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2823 AN: 10572

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13999 AN: 68006

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.130 Hom.: 669

Bravo AF: 0.133

Asia WGS AF: 0.0620 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.20
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: rs2228674; hg19: chr3-124770082;