rs3757930

Variant names:

• chr8-32731600-C-T
• rs3757930
• NM_013964.5:c.632+3522C>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.632+3522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,970 control chromosomes in the GnomAD database, including 10,078 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 0.36 (10078 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.632+3522C>T		intron_variant	Intron 6 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.632+3522C>T		intron_variant	Intron 6 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55062 AN: 151852 Hom.: 10064 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.363 AC: 55097 AN: 151970 Hom.: 10078 Cov.: 32 AF XY: 0.367 AC XY: 27248 AN XY: 74250

African (AFR) AF: 0.416 AC: 17220 AN: 41420

American (AMR) AF: 0.375 AC: 5734 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1895 AN: 5168

South Asian (SAS) AF: 0.305 AC: 1475 AN: 4830

European-Finnish (FIN) AF: 0.437 AC: 4598 AN: 10516

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21704 AN: 67980

Other (OTH) AF: 0.354 AC: 746 AN: 2108

Alfa AF: 0.336 Hom.: 10354

Bravo AF: 0.361

Asia WGS AF: 0.315 AC: 1099 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.51
PhyloP100		-0.41
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: rs3757930; hg19: chr8-32589118;