Variant 8-79766192-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000354724.8(HEY1):c.332-421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,529,534 control chromosomes in the GnomAD database, including 21,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1792 hom., cov: 33)

Exomes 𝑓: 0.17 ( 20012 hom. )

Consequence

HEY1
ENST00000354724.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.231

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 8-79766192-T-C is Benign according to our data. Variant chr8-79766192-T-C is described in ClinVar as [Benign]. Clinvar id is 1266917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HEY1	NM_012258.4 linkuse as main transcript	c.332-421A>G	intron_variant	ENST00000354724.8	NP_036390.3
HEY1	NM_001040708.2 linkuse as main transcript	c.344-421A>G	intron_variant		NP_001035798.1
HEY1	NM_001282851.2 linkuse as main transcript	c.61+11A>G	intron_variant		NP_001269780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEY1	ENST00000354724.8 linkuse as main transcript	c.332-421A>G		intron_variant		1	NM_012258.4	ENSP00000346761	P1	Q9Y5J3-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21195

AN:

152116

Hom.:

1787

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0489

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.0948

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.167

AC:

20875

AN:

124786

Hom.:

2011

AF XY:

0.160

AC XY:

10912

AN XY:

68274

show subpopulations

Gnomad AFR exome

AF:

0.0379

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.274

Gnomad SAS exome

AF:

0.0900

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.166

AC:

228588

AN:

1377300

Hom.:

20012

Cov.:

AF XY:

0.164

AC XY:

111233

AN XY:

679632

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.308

Gnomad4 SAS exome

AF:

0.0923

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.139

AC:

21212

AN:

152234

Hom.:

1792

Cov.:

AF XY:

0.137

AC XY:

10200

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0488

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.0938

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.120

Hom.:

314

Bravo

AF:

0.139

Asia WGS

AF:

0.222

AC:

774

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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