NM_013964.5:c.101-10990A>G

Variant names:

• chr8-32584838-A-G
• rs10954859
• NM_013964.5:c.101-10990A>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.101-10990A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,112 control chromosomes in the GnomAD database, including 5,122 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 0.26 (5122 hom., cov: 33)
• Consequence: NRG1 NM_013964.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• 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 (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG1	NM_013964.5	c.101-10990A>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.101-10990A>G		intron_variant	Intron 1 of 11	1	NM_013964.5	ENSP00000384620.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38976 AN: 151994 Hom.: 5118 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.256 AC: 39004 AN: 152112 Hom.: 5122 Cov.: 33 AF XY: 0.257 AC XY: 19104 AN XY: 74350

African (AFR) AF: 0.244 AC: 10111 AN: 41502

American (AMR) AF: 0.200 AC: 3050 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3470

East Asian (EAS) AF: 0.168 AC: 868 AN: 5178

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4820

European-Finnish (FIN) AF: 0.323 AC: 3408 AN: 10552

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18179 AN: 67988

Other (OTH) AF: 0.243 AC: 513 AN: 2112

Alfa AF: 0.247 Hom.: 2740

Bravo AF: 0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.74
PhyloP100		0.047
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: rs10954859; hg19: chr8-32442356;