rs6150532

Positions:

• chr8-32615241-ACTTTTT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000405005.8(NRG1):​c.451+681_451+686del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,000 control chromosomes in the GnomAD database, including 2,762 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (2762 hom., cov: 31)
• Consequence: NRG1 ENST00000405005.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.451+681_451+686del		intron_variant		ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.451+681_451+686del		intron_variant		1	NM_013964.5	ENSP00000384620	A2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19497 AN: 151882 Hom.: 2755 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.129 AC: 19545 AN: 152000 Hom.: 2762 Cov.: 31 AF XY: 0.135 AC XY: 10039 AN XY: 74330

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0824 Hom.: 183

Bravo AF: 0.158

Asia WGS AF: 0.257 AC: 893 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6150532; hg19: chr8-32472759;