Genetic Variant HEG1:p.Pro1348Pro (chr3-124970754-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020733.2(HEG1):c.4044G>A(p.Pro1348Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,610,542 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

HEG1
NM_020733.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

Variant links:

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]

HEG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-124970754-C-T is Benign according to our data. Variant chr3-124970754-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654089.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEG1	NM_020733.2 link	c.4044G>A	p.Pro1348Pro	synonymous_variant	Exon 17 of 17	ENST00000311127.9	NP_065784.1	Q9ULI3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEG1	ENST00000311127.9 link	c.4044G>A	p.Pro1348Pro	synonymous_variant	Exon 17 of 17	5	NM_020733.2	ENSP00000311502.3		Q9ULI3-1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.0903

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00111

AC:

270

AN:

242662

Hom.:

AF XY:

0.00115

AC XY:

151

AN XY:

131334

show subpopulations

Gnomad AFR exome

AF:

0.000471

Gnomad AMR exome

AF:

0.000236

Gnomad ASJ exome

AF:

0.00193

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.000546

Gnomad FIN exome

AF:

0.000800

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00159

AC:

2326

AN:

1458368

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1151

AN XY:

725000

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00281

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000611

Gnomad4 FIN exome

AF:

0.000751

Gnomad4 NFE exome

AF:

0.00185

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00145

AC:

220

AN:

152174

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00197

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HEG1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.2

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over