Variant 8-79765249-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000354724.8(HEY1):c.854C>T(p.Thr285Met) variant causes a missense change. The variant allele was found at a frequency of 0.00308 in 1,554,162 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 13 hom. )

Consequence

HEY1
ENST00000354724.8 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

HEY1 (HGNC:4880): (hes related family bHLH transcription factor with YRPW motif 1) This gene encodes a nuclear protein belonging to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcriptional repressors. Expression of this gene is induced by the Notch and c-Jun signal transduction pathways. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

HEY1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073598027).

BP6

Variant 8-79765249-G-A is Benign according to our data. Variant chr8-79765249-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041983.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 329 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HEY1	NM_012258.4 linkuse as main transcript	c.854C>T	p.Thr285Met	missense_variant	5/5	ENST00000354724.8	NP_036390.3
HEY1	NM_001040708.2 linkuse as main transcript	c.866C>T	p.Thr289Met	missense_variant	5/5		NP_001035798.1
HEY1	NM_001282851.2 linkuse as main transcript	c.584C>T	p.Thr195Met	missense_variant	2/2		NP_001269780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEY1	ENST00000354724.8 linkuse as main transcript	c.854C>T	p.Thr285Met	missense_variant	5/5	1	NM_012258.4	ENSP00000346761	P1	Q9Y5J3-1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00376

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00143

AC:

229

AN:

159810

Hom.:

AF XY:

0.00118

AC XY:

AN XY:

84070

show subpopulations

Gnomad AFR exome

AF:

0.000871

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.000708

Gnomad NFE exome

AF:

0.00276

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00318

AC:

4452

AN:

1401830

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

2109

AN XY:

691554

show subpopulations

Gnomad4 AFR exome

AF:

0.000690

Gnomad4 AMR exome

AF:

0.000949

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.000848

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152332

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00376

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.00400

AC:

ExAC

AF:

0.00108

AC:

116

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HEY1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;.;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0080

D;D;D

Sift4G

Benign

0.074

T;T;T

Polyphen

0.93

P;P;.

Vest4

0.34

MVP

0.23

MPC

0.79

ClinPred

0.031

GERP RS

5.8

Varity_R

0.072

gMVP

0.48

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