8-32571171-A-G

Variant names:

• chr8-32571171-A-G
• rs10503920
• NM_013964.5:c.100+22345A>G

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+22345A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,104 control chromosomes in the GnomAD database, including 7,565 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 0.29 (7565 hom., cov: 32)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.960
• Publications: 11 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.100+22345A>G		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+22345A>G		intron_variant	Intron 1 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43801 AN: 151986 Hom.: 7568 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.288 AC: 43811 AN: 152104 Hom.: 7565 Cov.: 32 AF XY: 0.291 AC XY: 21651 AN XY: 74342

African (AFR) AF: 0.160 AC: 6645 AN: 41516

American (AMR) AF: 0.251 AC: 3832 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3466

East Asian (EAS) AF: 0.794 AC: 4101 AN: 5162

South Asian (SAS) AF: 0.473 AC: 2277 AN: 4818

European-Finnish (FIN) AF: 0.265 AC: 2799 AN: 10578

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22130 AN: 67972

Other (OTH) AF: 0.292 AC: 618 AN: 2114

Alfa AF: 0.312 Hom.: 4546

Bravo AF: 0.282

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		0.96
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: rs10503920; hg19: chr8-32428689;