rs2207782

chr10-81997443-G-Achr10-81997443-G-C

Variant summary

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

The NM_001010848.4(NRG3):c.823+121280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,088 control chromosomes in the GnomAD database, including 20,158 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 0.46 (20158 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRG3	NM_001010848.4	c.823+121280G>A		intron_variant		ENST00000372141.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRG3	ENST00000372141.7	c.823+121280G>A		intron_variant		1	NM_001010848.4	A2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69558 AN: 151970 Hom.: 20102 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.458 AC: 69672 AN: 152088 Hom.: 20158 Cov.: 32 AF XY: 0.464 AC XY: 34466 AN XY: 74340

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.423

Alfa AF: 0.331 Hom.: 5288

Bravo AF: 0.491

Asia WGS AF: 0.600 AC: 2087 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.46
Dann	Benign	0.62

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: rs2207782; hg19: chr10-83757199;