8-32583717-C-A

Position:

• chr8-32583717-C-A

Variant summary

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

The NM_013964.5(NRG1):​c.101-12111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,216 control chromosomes in the GnomAD database, including 1,774 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 0.093 (1774 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.101-12111C>A		intron_variant		ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.101-12111C>A		intron_variant		1	NM_013964.5	ENSP00000384620	A2

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14062 AN: 152100 Hom.: 1769 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0925 AC: 14080 AN: 152216 Hom.: 1774 Cov.: 33 AF XY: 0.0951 AC XY: 7075 AN XY: 74422

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0814

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.0594

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0415 Hom.: 163

Bravo AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16879576; hg19: chr8-32441235;