Variant 8-32648114-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000520502.7(NRG1):c.397G>C(p.Val133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,614,138 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.024 ( 70 hom., cov: 32)

Exomes 𝑓: 0.018 ( 564 hom. )

Consequence

NRG1
ENST00000520502.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.83

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017232895).

BP6

Variant 8-32648114-G-C is Benign according to our data. Variant chr8-32648114-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 218702.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-32648114-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_013964.5 linkuse as main transcript	c.502+31229G>C		intron_variant		ENST00000405005.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000405005.8 linkuse as main transcript	c.502+31229G>C		intron_variant		1	NM_013964.5	A2	Q02297-1

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3636

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0611

Gnomad FIN

AF:

0.00462

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0502

GnomAD3 exomes

AF:

0.0244

AC:

6142

AN:

251484

Hom.:

170

AF XY:

0.0267

AC XY:

3631

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.0248

Gnomad ASJ exome

AF:

0.0364

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0648

Gnomad FIN exome

AF:

0.00360

Gnomad NFE exome

AF:

0.0184

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0184

AC:

26885

AN:

1461886

Hom.:

564

Cov.:

AF XY:

0.0201

AC XY:

14631

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0377

Gnomad4 AMR exome

AF:

0.0254

Gnomad4 ASJ exome

AF:

0.0382

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0621

Gnomad4 FIN exome

AF:

0.00356

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0238

AC:

3630

AN:

152252

Hom.:

Cov.:

AF XY:

0.0243

AC XY:

1807

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0337

Gnomad4 AMR

AF:

0.0282

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0605

Gnomad4 FIN

AF:

0.00462

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0497

Alfa

AF:

0.0199

Hom.:

Bravo

AF:

0.0253

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0174

AC:

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.0186

AC:

160

ExAC

AF:

0.0249

AC:

3022

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

EpiCase

AF:

0.0245

EpiControl

AF:

0.0264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Mar 06, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.19

Eigen_PC

Benign

0.0070

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.54

T;.

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;N

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.024

Sift

Benign

0.10

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.012

B;.

Vest4

0.050

MutPred

0.17

Gain of sheet (P = 0.0477);.;

ClinPred

0.0051

GERP RS

4.3

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