rs1937970

Variant names:

• chr10-82463710-A-G
• rs1937970
• NM_001010848.4:c.953+104842A>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.953+104842A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,086 control chromosomes in the GnomAD database, including 19,181 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 0.45 (19181 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.953+104842A>G		intron_variant	Intron 2 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.953+104842A>G		intron_variant	Intron 2 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68688 AN: 151968 Hom.: 19123 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.452 AC: 68803 AN: 152086 Hom.: 19181 Cov.: 32 AF XY: 0.449 AC XY: 33360 AN XY: 74340

African (AFR) AF: 0.782 AC: 32456 AN: 41498

American (AMR) AF: 0.459 AC: 7008 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3069 AN: 5154

South Asian (SAS) AF: 0.252 AC: 1217 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2788 AN: 10592

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20120 AN: 67974

Other (OTH) AF: 0.435 AC: 915 AN: 2102

Alfa AF: 0.352 Hom.: 34790

Bravo AF: 0.484

Asia WGS AF: 0.455 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.058
DANN	Benign	0.60
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1937970; hg19: chr10-84223466;