Variant ENST00000520407.5:c.191C>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.191C>T(p.Ser64Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,186,104 control chromosomes in the GnomAD database, including 2 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 not provided (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

NRG1
ENST00000520407.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.42

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=0.0076619685).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
NRG1	NM_013962.3 link	c.191C>T	p.Ser64Leu	missense_variant	Exon 1 of 5	NP_039256.2	Q02297-9
NRG1	XM_011544512.3 link	c.191C>T	p.Ser64Leu	missense_variant	Exon 1 of 13	XP_011542814.2
NRG1	XM_017013367.2 link	c.191C>T	p.Ser64Leu	missense_variant	Exon 1 of 11	XP_016868856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
NRG1	ENST00000520407.5 link	c.191C>T	p.Ser64Leu	missense_variant	Exon 1 of 5	1	ENSP00000434640.1	Q02297-9
NRG1	ENST00000650866.1 link	c.37+744C>T		intron_variant	Intron 1 of 12		ENSP00000499045.1	A0A494C1F5
NRG1	ENST00000652698.1 link	c.37+744C>T		intron_variant	Intron 1 of 11		ENSP00000499008.1	A0A494C1F8

Frequencies

GnomAD3 genomes

AF:

0.000128

AC:

AN:

148450

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000180

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000561

AC:

AN:

7136

Hom.:

AF XY:

0.000678

AC XY:

AN XY:

4422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000659

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000283

AC:

294

AN:

1037548

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

160

AN XY:

495684

show subpopulations

Gnomad4 AFR exome

AF:

0.0000487

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00327

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000228

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000128

AC:

AN:

148556

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

72408

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000180

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000265

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.00109

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Psychiatry Genetics Yale University

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.60

T;T

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.34

PROVEAN

Benign

-0.95

N;.

REVEL

Benign

0.25

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.011

D;D

Polyphen

0.16

B;.

Vest4

0.27

MutPred

0.21

Loss of glycosylation at S64 (P = 0.0037);Loss of glycosylation at S64 (P = 0.0037);

MVP

0.53

ClinPred

0.17

GERP RS

1.8

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