3-124970754-C-T

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

2

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]

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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
HEG1NM_020733.2 linkc.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
HEG1ENST00000311127.9 linkc.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.:
6
Cov.:
32
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.:
0
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.:
1
Cov.:
31
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.:
6
Cov.:
32
AF XY:
0.00133
AC XY:
99
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.:
0
Bravo
AF:
0.00197
Asia WGS
AF:
0.000577
AC:
2
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.

Other links and lift over

dbSNP: rs186255239; hg19: chr3-124689598; COSMIC: COSV60762799; API