chr10-82811513-T-C

Variant names:

• chr10-82811513-T-C
• rs17746658
• NM_001010848.4:c.1028-53898T>C

Variant summary

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

The NM_001010848.4(NRG3):​c.1028-53898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 152,280 control chromosomes in the GnomAD database, including 404 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 0.073 (404 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1028-53898T>C		intron_variant	Intron 3 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.1028-53898T>C		intron_variant	Intron 3 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11088 AN: 152162 Hom.: 403 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0728 AC: 11084 AN: 152280 Hom.: 404 Cov.: 32 AF XY: 0.0727 AC XY: 5413 AN XY: 74458

African (AFR) AF: 0.0637 AC: 2645 AN: 41542

American (AMR) AF: 0.0676 AC: 1035 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0475 AC: 229 AN: 4822

European-Finnish (FIN) AF: 0.104 AC: 1108 AN: 10612

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0823 AC: 5598 AN: 68028

Other (OTH) AF: 0.0704 AC: 149 AN: 2116

Alfa AF: 0.0752 Hom.: 67

Bravo AF: 0.0705

Asia WGS AF: 0.0240 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		2.2
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: rs17746658; hg19: chr10-84571269;