rs1317008

Variant names:

• chr10-82389534-C-T
• rs1317008
• NM_001010848.4:c.953+30666C>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.953+30666C>T 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 152,004 control chromosomes in the GnomAD database, including 15,302 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 (15302 hom., cov: 33)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• 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=-1.0).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	NM_001010848.4	MANE Select	c.953+30666C>T		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.953+30666C>T		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.953+30666C>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.953+30666C>T		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.953+30666C>T		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.443+30666C>T		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61548 AN: 151884 Hom.: 15254 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.406 AC: 61656 AN: 152004 Hom.: 15302 Cov.: 33 AF XY: 0.403 AC XY: 29943 AN XY: 74312

African (AFR) AF: 0.697 AC: 28889 AN: 41456

American (AMR) AF: 0.361 AC: 5510 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2806 AN: 5170

South Asian (SAS) AF: 0.204 AC: 983 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3251 AN: 10560

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

European-Non Finnish (NFE) AF: 0.268 AC: 18193 AN: 67944

Other (OTH) AF: 0.389 AC: 822 AN: 2112

Alfa AF: 0.299 Hom.: 4008

Bravo AF: 0.426

Asia WGS AF: 0.388 AC: 1346 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.45
PhyloP100		-0.55
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: rs1317008; hg19: chr10-84149290;