chr8-32767310-A-G

Variant names:

• chr8-32767310-A-G
• rs3735781
• NM_013964.5:c.*2908A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013964.5(NRG1):​c.*2908A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,992 control chromosomes in the GnomAD database, including 11,514 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 0.38 (11514 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: NRG1 NM_013964.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 11 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 (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.*2908A>G		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.*2908A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58435 AN: 151870 Hom.: 11496 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AF: 0.500 AC: 1 AN: 2

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: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.385 AC: 58490 AN: 151988 Hom.: 11514 Cov.: 32 AF XY: 0.376 AC XY: 27897 AN XY: 74256

African (AFR) AF: 0.386 AC: 15993 AN: 41426

American (AMR) AF: 0.307 AC: 4679 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1293 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1027 AN: 5166

South Asian (SAS) AF: 0.342 AC: 1646 AN: 4816

European-Finnish (FIN) AF: 0.338 AC: 3559 AN: 10542

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28857 AN: 68000

Other (OTH) AF: 0.402 AC: 848 AN: 2108

Alfa AF: 0.403 Hom.: 15775

Bravo AF: 0.379

Asia WGS AF: 0.298 AC: 1041 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	8.1
DANN	Benign	0.68
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs3735781; hg19: chr8-32624828;