rs7812662

Variant names:

• chr8-31668264-T-A
• rs7812662
• ENST00000520407.5:c.745+27535T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-31668264-T-A
• chr8-31668264-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520407.5(NRG1):​c.745+27535T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,996 control chromosomes in the GnomAD database, including 22,075 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22075 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.37+28833T>A		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.37+28833T>A		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.37+28833T>A		intron_variant	Intron 1 of 10		NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.745+27535T>A		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.304+27535T>A		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.37+28833T>A		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80219 AN: 151878 Hom.: 22059 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.598

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.528 AC: 80267 AN: 151996 Hom.: 22075 Cov.: 32 AF XY: 0.525 AC XY: 39003 AN XY: 74288

African (AFR) AF: 0.393 AC: 16285 AN: 41448

American (AMR) AF: 0.521 AC: 7962 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1971 AN: 5158

South Asian (SAS) AF: 0.423 AC: 2041 AN: 4824

European-Finnish (FIN) AF: 0.612 AC: 6452 AN: 10548

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.610 AC: 41439 AN: 67962

Other (OTH) AF: 0.597 AC: 1258 AN: 2108

Alfa AF: 0.562 Hom.: 3079

Bravo AF: 0.518

Asia WGS AF: 0.446 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7812662; hg19: chr8-31525780;