chr10-82908144-G-A

Variant names:

• chr10-82908144-G-A
• rs2078061
• NM_001010848.4:c.1054+42707G>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.1054+42707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,218 control chromosomes in the GnomAD database, including 1,090 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 0.082 (1090 hom., cov: 33)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1054+42707G>A		intron_variant	Intron 4 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.1054+42707G>A		intron_variant	Intron 4 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12494 AN: 152100 Hom.: 1079 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.00847

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0823 AC: 12534 AN: 152218 Hom.: 1090 Cov.: 33 AF XY: 0.0795 AC XY: 5919 AN XY: 74422

African (AFR) AF: 0.221 AC: 9171 AN: 41498

American (AMR) AF: 0.0555 AC: 849 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 323 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4824

European-Finnish (FIN) AF: 0.00847 AC: 90 AN: 10622

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1665 AN: 68012

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0653 Hom.: 134

Bravo AF: 0.0899

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.35
PhyloP100		-1.6
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: rs2078061; hg19: chr10-84667900;