8-32329564-C-T

Variant names:

• chr8-32329564-C-T
• rs7830691
• ENST00000520407.5:c.746-266264C>T

Variant summary

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

The ENST00000520407.5(NRG1):​c.746-266264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,912 control chromosomes in the GnomAD database, including 3,797 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 0.20 (3797 hom., cov: 31)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_001159999.3	c.38-266264C>T		intron_variant	Intron 1 of 12		NP_001153471.1
NRG1	NM_001159995.3	c.38-266264C>T		intron_variant	Intron 1 of 11		NP_001153467.1
NRG1	NM_001160001.3	c.38-266264C>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.746-266264C>T		intron_variant	Intron 1 of 4	1		ENSP00000434640.1
NRG1	ENST00000523534.5	c.305-266264C>T		intron_variant	Intron 1 of 12	5		ENSP00000429067.1
NRG1	ENST00000650866.1	c.38-266264C>T		intron_variant	Intron 1 of 12			ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30919 AN: 151792 Hom.: 3796 Cov.: 31

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.204 AC: 30916 AN: 151912 Hom.: 3797 Cov.: 31 AF XY: 0.199 AC XY: 14753 AN XY: 74242

African (AFR) AF: 0.0739 AC: 3061 AN: 41432

American (AMR) AF: 0.171 AC: 2605 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3466

East Asian (EAS) AF: 0.135 AC: 695 AN: 5148

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4808

European-Finnish (FIN) AF: 0.213 AC: 2245 AN: 10552

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.289 AC: 19623 AN: 67932

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.200 Hom.: 1265

Bravo AF: 0.193

Asia WGS AF: 0.205 AC: 709 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	2.8
DANN	Benign	0.57
PhyloP100		-0.38
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: rs7830691; hg19: chr8-32187080;