8-32595840-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_013964.5(NRG1):c.113G>A(p.Arg38Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,602,172 control chromosomes in the GnomAD database, including 132,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 9549 hom., cov: 32)

Exomes 𝑓: 0.40 ( 122776 hom. )

Consequence

NRG1
NM_013964.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.37

Publications

115 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia 6
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

NRG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0896198E-6).

BP6

Variant 8-32595840-G-A is Benign according to our data. Variant chr8-32595840-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059329.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NRG1	NM_013964.5	MANE Select	c.113G>A	p.Arg38Gln	missense	Exon 2 of 12	NP_039258.1
NRG1	NM_013956.5		c.113G>A	p.Arg38Gln	missense	Exon 2 of 13	NP_039250.2
NRG1	NM_013957.5		c.113G>A	p.Arg38Gln	missense	Exon 2 of 12	NP_039251.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NRG1	ENST00000405005.8	TSL:1 MANE Select	c.113G>A	p.Arg38Gln	missense	Exon 2 of 12	ENSP00000384620.2
NRG1	ENST00000287842.7	TSL:1	c.113G>A	p.Arg38Gln	missense	Exon 2 of 13	ENSP00000287842.4
NRG1	ENST00000356819.7	TSL:1	c.113G>A	p.Arg38Gln	missense	Exon 2 of 12	ENSP00000349275.6

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48749

AN:

151506

Hom.:

9560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.772

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.358

GnomAD2 exomes

AF:

0.399

AC:

98691

AN:

247262

AF XY:

0.401

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.377

GnomAD4 exome

AF:

0.402

AC:

583779

AN:

1450548

Hom.:

122776

Cov.:

AF XY:

0.402

AC XY:

289904

AN XY:

721876

show subpopulations

African (AFR)

AF:

0.0996

AC:

3257

AN:

32716

American (AMR)

AF:

0.431

AC:

18688

AN:

43334

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

9000

AN:

25532

East Asian (EAS)

AF:

0.774

AC:

30624

AN:

39546

South Asian (SAS)

AF:

0.410

AC:

34938

AN:

85318

European-Finnish (FIN)

AF:

0.342

AC:

17903

AN:

52356

Middle Eastern (MID)

AF:

0.339

AC:

1921

AN:

5666

European-Non Finnish (NFE)

AF:

0.401

AC:

443467

AN:

1106460

Other (OTH)

AF:

0.402

AC:

23981

AN:

59620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15590

31180

46769

62359

77949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13990

27980

41970

55960

69950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.321

AC:

48739

AN:

151624

Hom.:

9549

Cov.:

AF XY:

0.325

AC XY:

24041

AN XY:

74084

show subpopulations

African (AFR)

AF:

0.112

AC:

4647

AN:

41308

American (AMR)

AF:

0.370

AC:

5639

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1205

AN:

3472

East Asian (EAS)

AF:

0.771

AC:

3982

AN:

5162

South Asian (SAS)

AF:

0.426

AC:

2033

AN:

4770

European-Finnish (FIN)

AF:

0.348

AC:

3665

AN:

10524

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26463

AN:

67850

Other (OTH)

AF:

0.358

AC:

753

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1520

3041

4561

6082

7602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.378

Hom.:

53517

Bravo

AF:

0.319

TwinsUK

AF:

0.406

AC:

1505

ALSPAC

AF:

0.414

AC:

1595

ESP6500AA

AF:

0.133

AC:

586

ESP6500EA

AF:

0.396

AC:

3404

ExAC

AF:

0.390

AC:

47361

Asia WGS

AF:

0.547

AC:

1902

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NRG1-related disorder

Benign:1

Mar 27, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0000021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

PhyloP100

3.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

REVEL

Benign

0.042

Sift

Benign

0.044

Sift4G

Benign

0.074

Polyphen

0.70

Vest4

0.069

MPC

0.28

ClinPred

0.018

GERP RS

5.7

Varity_R

0.081

gMVP

0.32

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over