rs13257518

Variant names:

• chr8-32778056-T-A
• rs13257518
• ENST00000651335.1:c.941+17650T>A

Variant summary

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

The ENST00000651335.1(NRG1):​c.941+17650T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,158 control chromosomes in the GnomAD database, including 1,597 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 0.12 (1597 hom., cov: 32)
• Consequence: NRG1 ENST00000651335.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 3 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=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000651335.1	c.941+17650T>A		intron_variant	Intron 7 of 7			ENSP00000499047.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18986 AN: 152040 Hom.: 1597 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.125 AC: 18980 AN: 152158 Hom.: 1597 Cov.: 32 AF XY: 0.125 AC XY: 9292 AN XY: 74378

African (AFR) AF: 0.0305 AC: 1269 AN: 41556

American (AMR) AF: 0.108 AC: 1651 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.0653 AC: 315 AN: 4822

European-Finnish (FIN) AF: 0.222 AC: 2345 AN: 10562

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12505 AN: 67980

Other (OTH) AF: 0.131 AC: 276 AN: 2110

Alfa AF: 0.152 Hom.: 250

Bravo AF: 0.113

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.6
DANN	Benign	0.87
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs13257518; hg19: chr8-32635574;