rs13257518

chr8-32778056-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000651335.1(NRG1):c.942+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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000651335.1	c.942+17650T>A		intron_variant

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

Gnomad4 AFR AF: 0.0305

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0653

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.131

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13257518; hg19: chr8-32635574;