10-82959847-T-C

Position:

• chr10-82959847-T-C

Variant summary

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

The NM_001010848.4(NRG3):​c.1284+772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,050 control chromosomes in the GnomAD database, including 12,005 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 0.38 (12005 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

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]

NRG3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1284+772T>C		intron_variant		ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.1284+772T>C		intron_variant		1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58184 AN: 151930 Hom.: 12002 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.383 AC: 58208 AN: 152050 Hom.: 12005 Cov.: 32 AF XY: 0.378 AC XY: 28055 AN XY: 74312

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.429

Alfa AF: 0.415 Hom.: 1679

Bravo AF: 0.378

Asia WGS AF: 0.280 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.84

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: rs11816558; hg19: chr10-84719603;