8-32207846-G-T

Variant names:

• chr8-32207846-G-T
• rs1481747
• ENST00000520407.5:c.746-387982G>T

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-387982G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,154 control chromosomes in the GnomAD database, including 49,602 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 0.80 (49602 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-387982G>T		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-387982G>T		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-387982G>T		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.746-387982G>T		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-387982G>T		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-387982G>T		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121810 AN: 152038 Hom.: 49545 Cov.: 32

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.801 AC: 121923 AN: 152154 Hom.: 49602 Cov.: 32 AF XY: 0.798 AC XY: 59322 AN XY: 74370

African (AFR) AF: 0.922 AC: 38277 AN: 41528

American (AMR) AF: 0.864 AC: 13200 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2498 AN: 3466

East Asian (EAS) AF: 0.474 AC: 2449 AN: 5168

South Asian (SAS) AF: 0.714 AC: 3443 AN: 4824

European-Finnish (FIN) AF: 0.717 AC: 7590 AN: 10580

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.764 AC: 51915 AN: 67986

Other (OTH) AF: 0.795 AC: 1679 AN: 2112

Alfa AF: 0.806 Hom.: 7338

Bravo AF: 0.818

Asia WGS AF: 0.624 AC: 2172 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.51
PhyloP100		-0.26
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: rs1481747; hg19: chr8-32065362;