rs7005288

Variant names:

• chr8-32762949-A-G
• rs7005288
• NM_013964.5:c.1269-799A>G

Variant summary

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

The NM_013964.5(NRG1):​c.1269-799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,126 control chromosomes in the GnomAD database, including 3,303 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 0.18 (3303 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.1269-799A>G		intron_variant	Intron 11 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.1269-799A>G		intron_variant	Intron 11 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28064 AN: 152008 Hom.: 3300 Cov.: 32

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.184 AC: 28066 AN: 152126 Hom.: 3303 Cov.: 32 AF XY: 0.189 AC XY: 14029 AN XY: 74364

African (AFR) AF: 0.0665 AC: 2763 AN: 41542

American (AMR) AF: 0.297 AC: 4536 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2305 AN: 5144

South Asian (SAS) AF: 0.368 AC: 1770 AN: 4814

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10588

Middle Eastern (MID) AF: 0.286 AC: 83 AN: 290

European-Non Finnish (NFE) AF: 0.201 AC: 13679 AN: 67986

Other (OTH) AF: 0.217 AC: 458 AN: 2110

Alfa AF: 0.210 Hom.: 5470

Bravo AF: 0.191

Asia WGS AF: 0.370 AC: 1288 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		0.39
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: rs7005288; hg19: chr8-32620467;