Variant 15-75961970-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138573.4(NRG4):c.109G>A(p.Val37Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,607,010 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 61 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 51 hom. )

Consequence

NRG4
NM_138573.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0720

Variant links:

Genes affected

NRG4 (HGNC:29862): (neuregulin 4) The neuregulins, including NRG4, activate type-1 growth factor receptors (see EGFR; MIM 131550) to initiating cell-to-cell signaling through tyrosine phosphorylation (Harari et al., 1999 [PubMed 10348342]).[supplied by OMIM, Mar 2008]

NRG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030592084).

BP6

Variant 15-75961970-C-T is Benign according to our data. Variant chr15-75961970-C-T is described in ClinVar as [Benign]. Clinvar id is 783718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG4	NM_138573.4 linkuse as main transcript	c.109G>A	p.Val37Ile	missense_variant	4/6	ENST00000394907.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG4	ENST00000394907.8 linkuse as main transcript	c.109G>A	p.Val37Ile	missense_variant	4/6	1	NM_138573.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2381

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

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:

0.000338

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00417

AC:

1030

AN:

246886

Hom.:

AF XY:

0.00308

AC XY:

411

AN XY:

133460

show subpopulations

Gnomad AFR exome

AF:

0.0562

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.000202

Gnomad EAS exome

AF:

0.0000550

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00166

AC:

2418

AN:

1454778

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1044

AN XY:

723790

show subpopulations

Gnomad4 AFR exome

AF:

0.0562

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.0000772

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000165

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.0156

AC:

2382

AN:

152232

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1114

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0541

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0157

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.0176

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0535

AC:

235

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00508

AC:

617

Asia WGS

AF:

0.00231

AC:

AN:

3476

EpiCase

AF:

0.000329

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.6

DANN

Benign

0.15

DEOGEN2

Uncertain

0.50

D;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.076

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.41

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.022

Sift

Benign

0.44

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.0020

B;.

Vest4

0.22

MVP

0.014

MPC

0.22

ClinPred

0.0031

GERP RS

0.30

Varity_R

0.024

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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