Variant 8-31640156-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013962.3(NRG1):c.172G>A(p.Gly58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,176,150 control chromosomes in the GnomAD database, including 9,403 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1427 hom., cov: 32)

Exomes 𝑓: 0.12 ( 7976 hom. )

Consequence

NRG1
NM_013962.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.20

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021058023).

BP6

Variant 8-31640156-G-A is Benign according to our data. Variant chr8-31640156-G-A is described in ClinVar as [Benign]. Clinvar id is 1328708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
NRG1	NM_013962.3 linkuse as main transcript	c.172G>A	p.Gly58Arg	missense_variant	1/5	NP_039256.2	Q02297-9
NRG1	XM_011544512.3 linkuse as main transcript	c.172G>A	p.Gly58Arg	missense_variant	1/13	XP_011542814.2
NRG1	XM_017013367.2 linkuse as main transcript	c.172G>A	p.Gly58Arg	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.172G>A	p.Gly58Arg	missense_variant	1/5	1	ENSP00000434640.1	Q02297-9
NRG1	ENST00000650866.1 linkuse as main transcript	c.37+725G>A		intron_variant			ENSP00000499045.1	A0A494C1F5
NRG1	ENST00000652698.1 linkuse as main transcript	c.37+725G>A		intron_variant			ENSP00000499008.1	A0A494C1F8

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

19567

AN:

148312

Hom.:

1425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.0813

Gnomad EAS

AF:

0.00448

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.0865

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.141

AC:

827

AN:

5858

Hom.:

AF XY:

0.142

AC XY:

519

AN XY:

3650

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.0639

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.121

AC:

124639

AN:

1027736

Hom.:

7976

Cov.:

AF XY:

0.121

AC XY:

59254

AN XY:

489586

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.0705

Gnomad4 EAS exome

AF:

0.0103

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.132

AC:

19578

AN:

148414

Hom.:

1427

Cov.:

AF XY:

0.134

AC XY:

9659

AN XY:

72322

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.0813

Gnomad4 EAS

AF:

0.00450

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.136

Hom.:

192

ESP6500AA

AF:

0.105

AC:

150

ESP6500EA

AF:

0.0916

AC:

305

ExAC

AF:

0.0760

AC:

931

Asia WGS

AF:

0.0760

AC:

223

AN:

2930

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	clinical testing	GeneDx	Dec 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.50

N;.

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0

B;.

Vest4

0.10

MutPred

0.30

Gain of methylation at G58 (P = 0.0148);Gain of methylation at G58 (P = 0.0148);

ClinPred

0.082

GERP RS

1.4

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