8-32642221-T-C

Position:

• chr8-32642221-T-C

Variant summary

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

The NM_013964.5(NRG1):​c.502+25336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,038 control chromosomes in the GnomAD database, including 30,370 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 0.62 (30370 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.502+25336T>C		intron_variant		ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.502+25336T>C		intron_variant		1	NM_013964.5	ENSP00000384620	A2

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94522 AN: 151920 Hom.: 30322 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.622 AC: 94625 AN: 152038 Hom.: 30370 Cov.: 32 AF XY: 0.623 AC XY: 46247 AN XY: 74290

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.614

Alfa AF: 0.547 Hom.: 47561

Bravo AF: 0.638

Asia WGS AF: 0.566 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10095694; hg19: chr8-32499740;