rs17101017

Positions:

• chr10-82886356-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010848.4(NRG3):​c.1054+20919C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 152,182 control chromosomes in the GnomAD database, including 579 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 0.083 (579 hom., cov: 33)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG3	NM_001010848.4	c.1054+20919C>A		intron_variant		ENST00000372141.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG3	ENST00000372141.7	c.1054+20919C>A		intron_variant		1	NM_001010848.4	A2

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12555 AN: 152064 Hom.: 579 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.00983

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0823

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

GnomAD4 genome AF: 0.0827 AC: 12579 AN: 152182 Hom.: 579 Cov.: 33 AF XY: 0.0810 AC XY: 6029 AN XY: 74416

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.00966

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0595

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0779 Hom.: 157

Bravo AF: 0.0830

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs17101017; hg19: chr10-84646112;