rs2439272

Variant names:

• chr8-32635573-A-G
• rs2439272
• NM_013964.5:c.502+18688A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-32635573-A-G
• chr8-32635573-A-T

Variant summary

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

The NM_013964.5(NRG1):​c.502+18688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,912 control chromosomes in the GnomAD database, including 38,494 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 0.70 (38494 hom., cov: 31)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.502+18688A>G		intron_variant	Intron 5 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.502+18688A>G		intron_variant	Intron 5 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106660 AN: 151794 Hom.: 38439 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.703 AC: 106769 AN: 151912 Hom.: 38494 Cov.: 31 AF XY: 0.705 AC XY: 52303 AN XY: 74220

African (AFR) AF: 0.858 AC: 35594 AN: 41478

American (AMR) AF: 0.752 AC: 11472 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2254 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4072 AN: 5154

South Asian (SAS) AF: 0.606 AC: 2917 AN: 4816

European-Finnish (FIN) AF: 0.676 AC: 7098 AN: 10504

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41110 AN: 67912

Other (OTH) AF: 0.684 AC: 1444 AN: 2110

Alfa AF: 0.628 Hom.: 12801

Bravo AF: 0.720

Asia WGS AF: 0.676 AC: 2351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.90
DANN	Benign	0.76
PhyloP100		-0.56
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: rs2439272; hg19: chr8-32493092;