10-82296261-G-A

Variant names:

• chr10-82296261-G-A
• rs7921512
• NM_001010848.4:c.824-62478G>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.824-62478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,960 control chromosomes in the GnomAD database, including 20,771 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 0.48 (20771 hom., cov: 31)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010848.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	NM_001010848.4	MANE Select	c.824-62478G>A		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.824-62478G>A		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.824-62478G>A		intron	N/A	NP_001357010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	ENST00000372141.7	TSL:1 MANE Select	c.824-62478G>A		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.824-62478G>A		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.314-62478G>A		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72182 AN: 151842 Hom.: 20706 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.476 AC: 72318 AN: 151960 Hom.: 20771 Cov.: 31 AF XY: 0.470 AC XY: 34927 AN XY: 74284

African (AFR) AF: 0.812 AC: 33659 AN: 41476

American (AMR) AF: 0.420 AC: 6404 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2450 AN: 5132

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4814

European-Finnish (FIN) AF: 0.332 AC: 3502 AN: 10560

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22383 AN: 67944

Other (OTH) AF: 0.448 AC: 942 AN: 2104

Alfa AF: 0.407 Hom.: 3170

Bravo AF: 0.499

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.023
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: rs7921512; hg19: chr10-84056017;