Variant 8-31640296-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The ENST00000520407.5(NRG1):c.312G>A(p.Ala104Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000315 in 1,132,770 control chromosomes in the GnomAD database, including 1 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 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

NRG1
ENST00000520407.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.322

Variant links:

Genes affected

NRG1 (HGNC:7997): (neuregulin 1) The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016]

NRG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 8-31640296-G-A is Benign according to our data. Variant chr8-31640296-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 98387.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.322 with no splicing effect.

BS2

High AC in GnomAd4 at 206 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
NRG1	NM_013962.3 linkuse as main transcript	c.312G>A	p.Ala104Ala	synonymous_variant	1/5	NP_039256.2	Q02297-9
NRG1	XM_011544512.3 linkuse as main transcript	c.312G>A	p.Ala104Ala	synonymous_variant	1/13	XP_011542814.2
NRG1	XM_017013367.2 linkuse as main transcript	c.312G>A	p.Ala104Ala	synonymous_variant	1/11	XP_016868856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
NRG1	ENST00000520407.5 linkuse as main transcript	c.312G>A	p.Ala104Ala	synonymous_variant	1/5	1	ENSP00000434640.1	Q02297-9
NRG1	ENST00000650866.1 linkuse as main transcript	c.37+865G>A		intron_variant			ENSP00000499045.1	A0A494C1F5
NRG1	ENST00000652698.1 linkuse as main transcript	c.37+865G>A		intron_variant			ENSP00000499008.1	A0A494C1F8

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

205

AN:

148074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000201

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000301

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

151

AN:

984592

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

463962

show subpopulations

Gnomad4 AFR exome

AF:

0.00666

Gnomad4 AMR exome

AF:

0.000186

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000523

GnomAD4 genome

AF:

0.00139

AC:

206

AN:

148178

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

72198

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.000201

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000301

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00149

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	NRG1: BP4, BP7 -
not provided, no classification provided	literature only	Psychiatry Genetics Yale University	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

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