10-82221414-C-G

Variant names:

• chr10-82221414-C-G
• rs1336294
• NM_001010848.4:c.824-137325C>G

Variant summary

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

The NM_001010848.4(NRG3):​c.824-137325C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,158 control chromosomes in the GnomAD database, including 907 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 0.11 (907 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.824-137325C>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.824-137325C>G		intron_variant	Intron 1 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15968 AN: 152040 Hom.: 906 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0101

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.105 AC: 15979 AN: 152158 Hom.: 907 Cov.: 32 AF XY: 0.107 AC XY: 7941 AN XY: 74378

African (AFR) AF: 0.145 AC: 6017 AN: 41522

American (AMR) AF: 0.0959 AC: 1466 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3468

East Asian (EAS) AF: 0.00988 AC: 51 AN: 5162

South Asian (SAS) AF: 0.149 AC: 718 AN: 4818

European-Finnish (FIN) AF: 0.113 AC: 1196 AN: 10572

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0853 AC: 5803 AN: 68012

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.0311 Hom.: 17

Bravo AF: 0.0996

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.043
DANN	Benign	0.85
PhyloP100		-1.3
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: rs1336294; hg19: chr10-83981170;