rs2919390

Variant names:

• chr8-32669436-A-C
• rs2919390
• NM_013964.5:c.502+52551A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-32669436-A-C
• chr8-32669436-A-T

Variant summary

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

The NM_013964.5(NRG1):​c.502+52551A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,928 control chromosomes in the GnomAD database, including 14,692 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 0.43 (14692 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_013964.5	MANE Select	c.502+52551A>C		intron	N/A	NP_039258.1
	NRG1	NM_001322205.2		c.667+21052A>C		intron	N/A	NP_001309134.1
	NRG1	NM_013956.5		c.502+52551A>C		intron	N/A	NP_039250.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000405005.8	TSL:1 MANE Select	c.502+52551A>C		intron	N/A	ENSP00000384620.2
	NRG1	ENST00000287842.7	TSL:1	c.502+52551A>C		intron	N/A	ENSP00000287842.4
	NRG1	ENST00000356819.7	TSL:1	c.502+52551A>C		intron	N/A	ENSP00000349275.6

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65145 AN: 151812 Hom.: 14673 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.429 AC: 65211 AN: 151928 Hom.: 14692 Cov.: 32 AF XY: 0.436 AC XY: 32399 AN XY: 74264

African (AFR) AF: 0.383 AC: 15884 AN: 41432

American (AMR) AF: 0.524 AC: 7996 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3466

East Asian (EAS) AF: 0.846 AC: 4362 AN: 5154

South Asian (SAS) AF: 0.424 AC: 2039 AN: 4814

European-Finnish (FIN) AF: 0.486 AC: 5127 AN: 10548

Middle Eastern (MID) AF: 0.293 AC: 85 AN: 290

European-Non Finnish (NFE) AF: 0.402 AC: 27322 AN: 67934

Other (OTH) AF: 0.402 AC: 849 AN: 2112

Alfa AF: 0.411 Hom.: 46053

Bravo AF: 0.435

Asia WGS AF: 0.590 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.46
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2919390; hg19: chr8-32526955;