Variant chr8-79766258-AGGCATGT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001282851.2(HEY1):c.-2_5delACATGCC(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,530,764 control chromosomes in the GnomAD database, including 11,511 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1270 hom., cov: 31)

Exomes 𝑓: 0.11 ( 10241 hom. )

Consequence

HEY1
NM_001282851.2 frameshift, start_lost

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.792

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 -10 ACMG points.

BP6

Variant 8-79766258-AGGCATGT-A is Benign according to our data. Variant chr8-79766258-AGGCATGT-A is described in ClinVar as [Benign]. Clinvar id is 1232147.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEY1	NM_012258.4 link	c.331+386_331+392delACATGCC		intron_variant	Intron 4 of 4	ENST00000354724.8	NP_036390.3	Q9Y5J3-1
HEY1	NM_001282851.2 link	c.-2_5delACATGCC	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 2		NP_001269780.1	Q9Y5J3B4DEI9
HEY1	NM_001282851.2 link	c.-2_5delACATGCC		5_prime_UTR_variant	Exon 1 of 2		NP_001269780.1	Q9Y5J3B4DEI9
HEY1	NM_001040708.2 link	c.343+386_343+392delACATGCC		intron_variant	Intron 4 of 4		NP_001035798.1	Q9Y5J3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEY1	ENST00000354724.8 link	c.331+386_331+392delACATGCC		intron_variant	Intron 4 of 4	1	NM_012258.4	ENSP00000346761.3		Q9Y5J3-1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18786

AN:

152010

Hom.:

1274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0901

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.0733

AC:

8601

AN:

117348

Hom.:

704

AF XY:

0.0841

AC XY:

5386

AN XY:

64036

show subpopulations

Gnomad AFR exome

AF:

0.0507

Gnomad AMR exome

AF:

0.0334

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.000481

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0608

Gnomad OTH exome

AF:

0.0774

GnomAD4 exome

AF:

0.113

AC:

155102

AN:

1378634

Hom.:

10241

AF XY:

0.117

AC XY:

79646

AN XY:

680170

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.0671

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.000840

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.123

AC:

18784

AN:

152130

Hom.:

1270

Cov.:

AF XY:

0.126

AC XY:

9375

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.0898

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.122

Hom.:

235

Bravo

AF:

0.116

Asia WGS

AF:

0.113

AC:

394

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HEY1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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