rs17101017

Variant names:

• chr10-82886356-C-A
• rs17101017
• NM_001010848.4:c.1054+20919C>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+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
• Publications: 3 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=-0.81).
• 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 rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1054+20919C>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+20919C>A		intron_variant	Intron 4 of 8	1	NM_001010848.4	ENSP00000361214.2

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

African (AFR) AF: 0.127 AC: 5257 AN: 41508

American (AMR) AF: 0.0462 AC: 706 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3472

East Asian (EAS) AF: 0.00966 AC: 50 AN: 5176

South Asian (SAS) AF: 0.0499 AC: 240 AN: 4810

European-Finnish (FIN) AF: 0.0595 AC: 631 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5082 AN: 68006

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.0787 Hom.: 192

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
PhyloP100		0.069
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: rs17101017; hg19: chr10-84646112;