8-32460839-T-C

Position:

• chr8-32460839-T-C

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-134989T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,896 control chromosomes in the GnomAD database, including 20,311 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 0.51 (20311 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG1	NM_001159995.3	c.38-134989T>C		intron_variant
NRG1	NM_001159999.3	c.38-134989T>C		intron_variant
NRG1	NM_001160001.3	c.38-134989T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG1	ENST00000520407.5	c.746-134989T>C		intron_variant		1
NRG1	ENST00000519301.6	c.38-134989T>C		intron_variant		5
NRG1	ENST00000523534.5	c.305-134989T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77806 AN: 151776 Hom.: 20288 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.513 AC: 77879 AN: 151896 Hom.: 20311 Cov.: 32 AF XY: 0.514 AC XY: 38143 AN XY: 74222

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.509

Alfa AF: 0.523 Hom.: 4613

Bravo AF: 0.512

Asia WGS AF: 0.441 AC: 1533 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12542743; hg19: chr8-32318355; COSMIC: COSV73060619;