chr10-82128587-G-T

Variant names:

• chr10-82128587-G-T
• rs10490933
• NM_001010848.4:c.824-230152G>T

Variant summary

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

The NM_001010848.4(NRG3):​c.824-230152G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 152,080 control chromosomes in the GnomAD database, including 134 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 0.021 (134 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 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.824-230152G>T		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.824-230152G>T		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.824-230152G>T		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.824-230152G>T		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.824-230152G>T		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.136-38140G>T		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3104 AN: 151964 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.00809

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00202

Gnomad OTH AF: 0.0260

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

GnomAD4 genome AF: 0.0206 AC: 3126 AN: 152080 Hom.: 134 Cov.: 32 AF XY: 0.0220 AC XY: 1636 AN XY: 74356

African (AFR) AF: 0.0231 AC: 959 AN: 41516

American (AMR) AF: 0.0763 AC: 1163 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00809 AC: 28 AN: 3462

East Asian (EAS) AF: 0.142 AC: 735 AN: 5172

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00202 AC: 137 AN: 67960

Other (OTH) AF: 0.0262 AC: 55 AN: 2102

Alfa AF: 0.0101 Hom.: 107

Bravo AF: 0.0290

Asia WGS AF: 0.0660 AC: 227 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.60
PhyloP100		-0.34
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: rs10490933; hg19: chr10-83888343;