rs3735782

Positions:

• chr8-32767339-C-A
• chr8-32767339-C-T

Variant summary

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

The NM_013964.5(NRG1):​c.*2937C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,942 control chromosomes in the GnomAD database, including 13,973 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 0.42 (13973 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NRG1 NM_013964.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG1	NM_013964.5	c.*2937C>A		3_prime_UTR_variant	12/12	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.*2937C>A		3_prime_UTR_variant	12/12	1	NM_013964.5	ENSP00000384620	A2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63403 AN: 151822 Hom.: 13973 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.452

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.417 AC: 63411 AN: 151942 Hom.: 13973 Cov.: 32 AF XY: 0.422 AC XY: 31339 AN XY: 74226

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.448

Alfa AF: 0.439 Hom.: 8104

Bravo AF: 0.410

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3735782; hg19: chr8-32624857;