rs1080293

Variant names:

• chr10-82136504-A-G
• rs1080293
• NM_001010848.4:c.824-222235A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-82136504-A-G
• chr10-82136504-A-T

Variant summary

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

The NM_001010848.4(NRG3):​c.824-222235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,048 control chromosomes in the GnomAD database, including 38,151 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 0.70 (38151 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.824-222235A>G		intron_variant	Intron 1 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.824-222235A>G		intron_variant	Intron 1 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106486 AN: 151930 Hom.: 38139 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.701 AC: 106535 AN: 152048 Hom.: 38151 Cov.: 32 AF XY: 0.698 AC XY: 51885 AN XY: 74296

African (AFR) AF: 0.564 AC: 23421 AN: 41492

American (AMR) AF: 0.615 AC: 9386 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2841 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2738 AN: 5136

South Asian (SAS) AF: 0.639 AC: 3073 AN: 4810

European-Finnish (FIN) AF: 0.792 AC: 8377 AN: 10578

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54414 AN: 67974

Other (OTH) AF: 0.711 AC: 1502 AN: 2112

Alfa AF: 0.773 Hom.: 26717

Bravo AF: 0.683

Asia WGS AF: 0.600 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.83
DANN	Benign	0.83
PhyloP100		-0.54
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: rs1080293; hg19: chr10-83896260;