rs3802160

Variant names:

• chr8-32547111-A-G
• rs3802160
• ENST00000520407.5:c.746-48717A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-32547111-A-G
• chr8-32547111-A-T

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-48717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,054 control chromosomes in the GnomAD database, including 12,738 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 0.39 (12738 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-48717A>G		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-48717A>G		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-48717A>G		intron_variant	Intron 1 of 10		NP_001153473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000520407.5	c.746-48717A>G		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-48717A>G		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-48717A>G		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59499 AN: 151936 Hom.: 12731 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.392 AC: 59530 AN: 152054 Hom.: 12738 Cov.: 32 AF XY: 0.395 AC XY: 29332 AN XY: 74352

African (AFR) AF: 0.228 AC: 9465 AN: 41496

American (AMR) AF: 0.486 AC: 7435 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3466

East Asian (EAS) AF: 0.178 AC: 917 AN: 5154

South Asian (SAS) AF: 0.408 AC: 1963 AN: 4814

European-Finnish (FIN) AF: 0.558 AC: 5888 AN: 10556

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31186 AN: 67966

Other (OTH) AF: 0.388 AC: 817 AN: 2108

Alfa AF: 0.412 Hom.: 1748

Bravo AF: 0.378

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		0.56
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: rs3802160; hg19: chr8-32404629;