chr8-32767339-C-A

Variant names:

• chr8-32767339-C-A
• rs3735782
• NM_013964.5:c.*2937C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

NRG1 Gene-Disease associations (from GenCC):

• schizophrenia 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.*2937C>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.*2937C>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_013964.5	ENSP00000384620.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.261 AC: 10818 AN: 41424

American (AMR) AF: 0.481 AC: 7342 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3468

East Asian (EAS) AF: 0.448 AC: 2307 AN: 5150

South Asian (SAS) AF: 0.502 AC: 2424 AN: 4826

European-Finnish (FIN) AF: 0.476 AC: 5024 AN: 10546

Middle Eastern (MID) AF: 0.462 AC: 134 AN: 290

European-Non Finnish (NFE) AF: 0.474 AC: 32217 AN: 67956

Other (OTH) AF: 0.448 AC: 944 AN: 2106

Alfa AF: 0.440 Hom.: 8998

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
PhyloP100		0.61

Splicing

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

Other links and lift over

dbSNP: rs3735782; hg19: chr8-32624857;