Variant 8-31640334-C-T 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.350C>T(p.Pro117Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,183,460 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 33 hom. )

Consequence

NRG1
ENST00000520407.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.333

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=0.0071258247).

BS2

High AC in GnomAd at 761 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
NRG1	NM_013962.3 linkuse as main transcript	c.350C>T	p.Pro117Leu	missense_variant	1/5
NRG1	XM_011544512.3 linkuse as main transcript	c.350C>T	p.Pro117Leu	missense_variant	1/13
NRG1	XM_017013367.2 linkuse as main transcript	c.350C>T	p.Pro117Leu	missense_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
NRG1	ENST00000520407.5 linkuse as main transcript	c.350C>T	p.Pro117Leu	missense_variant	1/5	1	Q02297-9
NRG1	ENST00000519301.6 linkuse as main transcript	c.37+903C>T		intron_variant		5	Q02297-11
NRG1	ENST00000650866.1 linkuse as main transcript	c.37+903C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

761

AN:

148858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000934

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.00389

Gnomad OTH

AF:

0.00292

GnomAD3 exomes

AF:

0.0298

AC:

AN:

336

Hom.:

AF XY:

0.0326

AC XY:

AN XY:

184

show subpopulations

Gnomad FIN exome

AF:

0.0652

Gnomad NFE exome

AF:

0.00515

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00416

AC:

4306

AN:

1034500

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

1994

AN XY:

488960

show subpopulations

Gnomad4 AFR exome

AF:

0.000715

Gnomad4 AMR exome

AF:

0.00147

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000884

Gnomad4 FIN exome

AF:

0.0411

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00271

GnomAD4 genome

AF:

0.00512

AC:

762

AN:

148960

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

507

AN XY:

72650

show subpopulations

Gnomad4 AFR

AF:

0.000461

Gnomad4 AMR

AF:

0.000933

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.00389

Gnomad4 OTH

AF:

0.00289

Alfa

AF:

0.00381

Hom.:

Bravo

AF:

0.00186

ExAC

AF:

0.00203

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

-0.45

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.47

T;T

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.12

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.019

D;T

Polyphen

0.062

B;.

Vest4

0.18

ClinPred

0.078

GERP RS

-1.5

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