Variant 8-31639995-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000520407.5(NRG1):c.11G>C(p.Arg4Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000448 in 1,124,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

NRG1
ENST00000520407.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 3.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021544874).

BS2

High AC in GnomAd4 at 83 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
NRG1	NM_013962.3 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/5	NP_039256.2	Q02297-9
NRG1	XM_011544512.3 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/13	XP_011542814.2
NRG1	XM_017013367.2 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_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.11G>C	p.Arg4Pro	missense_variant	1/5	1	ENSP00000434640.1	Q02297-9
NRG1	ENST00000650866.1 linkuse as main transcript	c.37+564G>C		intron_variant			ENSP00000499045.1	A0A494C1F5
NRG1	ENST00000652698.1 linkuse as main transcript	c.37+564G>C		intron_variant			ENSP00000499008.1	A0A494C1F8

Frequencies

GnomAD3 genomes

AF:

0.000548

AC:

AN:

149538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000932

Gnomad ASJ

AF:

0.00348

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000729

Gnomad OTH

AF:

0.000486

GnomAD3 exomes

AF:

0.00116

AC:

AN:

6882

Hom.:

AF XY:

0.000834

AC XY:

AN XY:

3596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00617

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00725

GnomAD4 exome

AF:

0.000432

AC:

421

AN:

975198

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

208

AN XY:

459736

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000397

Gnomad4 ASJ exome

AF:

0.00336

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000107

Gnomad4 FIN exome

AF:

0.0000675

Gnomad4 NFE exome

AF:

0.000404

Gnomad4 OTH exome

AF:

0.000667

GnomAD4 genome

AF:

0.000555

AC:

AN:

149644

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

AN XY:

73052

show subpopulations

Gnomad4 AFR

AF:

0.0000727

Gnomad4 AMR

AF:

0.000931

Gnomad4 ASJ

AF:

0.00348

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000729

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.0000532

Hom.:

Bravo

AF:

0.000680

ExAC

AF:

0.000108

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

Psychiatry Genetics Yale University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

0.064

Eigen_PC

Benign

0.047

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.47

T;T

M_CAP

Pathogenic

1.0

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

0.79

N;.

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.90

P;.

Vest4

0.53

MVP

0.44

ClinPred

0.24

GERP RS

2.0

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