Variant 8-31640283-AGGC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_013962.3(NRG1):c.314_316delCGG(p.Ala105del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000936 in 1,108,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

NRG1
NM_013962.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 8-31640283-AGGC-A is Benign according to our data. Variant chr8-31640283-AGGC-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038071.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
NRG1	NM_013962.3 link	c.314_316delCGG	p.Ala105del	disruptive_inframe_deletion	Exon 1 of 5	NP_039256.2	Q02297-9
NRG1	XM_011544512.3 link	c.314_316delCGG	p.Ala105del	disruptive_inframe_deletion	Exon 1 of 13	XP_011542814.2
NRG1	XM_017013367.2 link	c.314_316delCGG	p.Ala105del	disruptive_inframe_deletion	Exon 1 of 11	XP_016868856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
NRG1	ENST00000520407.5 link	c.314_316delCGG	p.Ala105del	disruptive_inframe_deletion	Exon 1 of 5	1	ENSP00000434640.1	Q02297-9
NRG1	ENST00000650866.1 link	c.37+867_37+869delCGG		intron_variant	Intron 1 of 12		ENSP00000499045.1	A0A494C1F5
NRG1	ENST00000652698.1 link	c.37+867_37+869delCGG		intron_variant	Intron 1 of 11		ENSP00000499008.1	A0A494C1F8

Frequencies

GnomAD3 genomes

AF:

0.0000407

AC:

AN:

147334

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000489

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:

0.000111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000453

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00107

AC:

1032

AN:

961094

Hom.:

AF XY:

0.00114

AC XY:

518

AN XY:

452742

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00538

Gnomad4 ASJ exome

AF:

0.00386

Gnomad4 EAS exome

AF:

0.00631

Gnomad4 SAS exome

AF:

0.000436

Gnomad4 FIN exome

AF:

0.00753

Gnomad4 NFE exome

AF:

0.000785

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.0000407

AC:

AN:

147334

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71714

show subpopulations

Gnomad4 AFR

AF:

0.0000489

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000111

Gnomad4 NFE

AF:

0.0000453

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NRG1-related disorder

Benign:1

Jul 17, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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