10-82191935-G-A

Variant names:

• chr10-82191935-G-A
• rs1649942
• NM_001010848.4:c.824-166804G>A

Variant summary

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

The NM_001010848.4(NRG3):​c.824-166804G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,030 control chromosomes in the GnomAD database, including 40,903 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 0.73 (40903 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 17 publications found

Genes affected

NRG3 (HGNC:7999): (neuregulin 3) This gene is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4 - members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but their biological validity has not been verified.[provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010848.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	NM_001010848.4	MANE Select	c.824-166804G>A		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.824-166804G>A		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.824-166804G>A		intron	N/A	NP_001357010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	ENST00000372141.7	TSL:1 MANE Select	c.824-166804G>A		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.824-166804G>A		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.235+25109G>A		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111294 AN: 151912 Hom.: 40886 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.732 AC: 111355 AN: 152030 Hom.: 40903 Cov.: 32 AF XY: 0.733 AC XY: 54462 AN XY: 74302

African (AFR) AF: 0.684 AC: 28352 AN: 41466

American (AMR) AF: 0.735 AC: 11226 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2770 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4124 AN: 5160

South Asian (SAS) AF: 0.845 AC: 4076 AN: 4822

European-Finnish (FIN) AF: 0.728 AC: 7682 AN: 10548

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50708 AN: 67984

Other (OTH) AF: 0.727 AC: 1532 AN: 2106

Alfa AF: 0.745 Hom.: 169665

Bravo AF: 0.729

Asia WGS AF: 0.824 AC: 2864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.013
DANN	Benign	0.66
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1649942; hg19: chr10-83951691;