NM_001010848.4:c.953+108240A>C

Variant names:

• chr10-82467108-A-C
• rs1937971
• NM_001010848.4:c.953+108240A>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.953+108240A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,914 control chromosomes in the GnomAD database, including 17,613 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 0.44 (17613 hom., cov: 31)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 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.953+108240A>C		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.953+108240A>C		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.953+108240A>C		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.953+108240A>C		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.953+108240A>C		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.443+108240A>C		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66502 AN: 151796 Hom.: 17555 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.439 AC: 66616 AN: 151914 Hom.: 17613 Cov.: 31 AF XY: 0.435 AC XY: 32282 AN XY: 74266

African (AFR) AF: 0.736 AC: 30459 AN: 41404

American (AMR) AF: 0.455 AC: 6950 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3466

East Asian (EAS) AF: 0.594 AC: 3047 AN: 5126

South Asian (SAS) AF: 0.252 AC: 1212 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2773 AN: 10582

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20046 AN: 67948

Other (OTH) AF: 0.427 AC: 900 AN: 2108

Alfa AF: 0.414 Hom.: 2463

Bravo AF: 0.469

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.032
DANN	Benign	0.43
PhyloP100		-3.9
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: rs1937971; hg19: chr10-84226864;