10-82393234-A-G

Variant names:

• chr10-82393234-A-G
• rs1937984
• NM_001010848.4:c.953+34366A>G

Variant summary

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

The NM_001010848.4(NRG3):​c.953+34366A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,884 control chromosomes in the GnomAD database, including 15,311 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 0.41 (15311 hom., cov: 31)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 4 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 = 0.69 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	NM_001010848.4	MANE Select	c.953+34366A>G		intron	N/A	NP_001010848.2	P56975-4
	NRG3	NM_001370084.1		c.953+34366A>G		intron	N/A	NP_001357013.1	D9ZHP6
	NRG3	NM_001370081.1		c.953+34366A>G		intron	N/A	NP_001357010.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	ENST00000372141.7	TSL:1 MANE Select	c.953+34366A>G		intron	N/A	ENSP00000361214.2	P56975-4
	NRG3	ENST00000404547.5	TSL:1	c.953+34366A>G		intron	N/A	ENSP00000384796.1	P56975-1
	NRG3	ENST00000556918.5	TSL:1	c.443+34366A>G		intron	N/A	ENSP00000451376.1	D9ZHQ7

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61485 AN: 151766 Hom.: 15263 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.406 AC: 61592 AN: 151884 Hom.: 15311 Cov.: 31 AF XY: 0.403 AC XY: 29907 AN XY: 74226

African (AFR) AF: 0.697 AC: 28851 AN: 41416

American (AMR) AF: 0.362 AC: 5518 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3472

East Asian (EAS) AF: 0.560 AC: 2863 AN: 5116

South Asian (SAS) AF: 0.199 AC: 960 AN: 4816

European-Finnish (FIN) AF: 0.303 AC: 3200 AN: 10564

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18210 AN: 67946

Other (OTH) AF: 0.387 AC: 816 AN: 2106

Alfa AF: 0.304 Hom.: 13181

Bravo AF: 0.426

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.69
PhyloP100		0.15
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: rs1937984; hg19: chr10-84152990;