8-32558756-G-A

Variant names:

• chr8-32558756-G-A
• rs7825175
• NM_013964.5:c.100+9930G>A

Variant summary

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

The NM_013964.5(NRG1):​c.100+9930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,032 control chromosomes in the GnomAD database, including 2,591 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 0.18 (2591 hom., cov: 31)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 22 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.100+9930G>A		intron_variant	Intron 1 of 11	ENST00000405005.8	NP_039258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG1	ENST00000405005.8	c.100+9930G>A		intron_variant	Intron 1 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27303 AN: 151914 Hom.: 2593 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.180 AC: 27311 AN: 152032 Hom.: 2591 Cov.: 31 AF XY: 0.179 AC XY: 13342 AN XY: 74332

African (AFR) AF: 0.136 AC: 5632 AN: 41482

American (AMR) AF: 0.148 AC: 2261 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3470

East Asian (EAS) AF: 0.119 AC: 615 AN: 5156

South Asian (SAS) AF: 0.191 AC: 922 AN: 4816

European-Finnish (FIN) AF: 0.249 AC: 2629 AN: 10560

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13979 AN: 67952

Other (OTH) AF: 0.171 AC: 361 AN: 2110

Alfa AF: 0.191 Hom.: 11709

Bravo AF: 0.168

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		-0.41
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: rs7825175; hg19: chr8-32416274;