Variant 8-32605615-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_013964.5(NRG1):c.332T>C(p.Met111Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

NRG1
NM_013964.5 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 0.865

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11741188).

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5 linkuse as main transcript	c.332T>C	p.Met111Thr	missense_variant	3/12	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8 linkuse as main transcript	c.332T>C	p.Met111Thr	missense_variant	3/12	1	NM_013964.5	ENSP00000384620	A2	Q02297-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250816

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135524

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:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461262

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000279

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Other:1

Affects, no assertion criteria provided

research

Yunnan Provincial Key Laboratory of Clinical Virology, Institution of Basic and Clinical Medicine of Yunnan Province, The First People's Hospital of Yunnan Province

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.21

.;.;.;T;.;.;.;.;.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.84

.;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.12

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.5

.;.;.;.;.;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.50

N;N;N;N;.;N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;T;T;T;.;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T;T

Polyphen

0.033, 0.0010, 0.0040, 0.016

.;.;B;.;.;.;B;B;B;B

Vest4

0.79, 0.68, 0.60, 0.57, 0.53, 0.68, 0.58

MutPred

0.50

.;.;.;.;.;Gain of phosphorylation at M111 (P = 0.0649);Gain of phosphorylation at M111 (P = 0.0649);Gain of phosphorylation at M111 (P = 0.0649);Gain of phosphorylation at M111 (P = 0.0649);Gain of phosphorylation at M111 (P = 0.0649);

MVP

0.72

MPC

0.25

ClinPred

0.027

GERP RS

3.4

Varity_R

0.042

gMVP

0.40

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