10-82959847-T-C

Variant names:

• chr10-82959847-T-C
• rs11816558
• NM_001010848.4:c.1284+772T>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.1284+772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,050 control chromosomes in the GnomAD database, including 12,005 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 0.38 (12005 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 0 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 (NFE) allele frequency at 95% confidence interval = 0.472 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.1284+772T>C		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.1284+772T>C		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.1281+772T>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.1284+772T>C		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.1284+772T>C		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.774+772T>C		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58184 AN: 151930 Hom.: 12002 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.383 AC: 58208 AN: 152050 Hom.: 12005 Cov.: 32 AF XY: 0.378 AC XY: 28055 AN XY: 74312

African (AFR) AF: 0.249 AC: 10319 AN: 41484

American (AMR) AF: 0.373 AC: 5699 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3472

East Asian (EAS) AF: 0.211 AC: 1090 AN: 5174

South Asian (SAS) AF: 0.303 AC: 1461 AN: 4814

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10560

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32382 AN: 67954

Other (OTH) AF: 0.429 AC: 904 AN: 2108

Alfa AF: 0.409 Hom.: 1709

Bravo AF: 0.378

Asia WGS AF: 0.280 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.84
PhyloP100		-0.089
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: rs11816558; hg19: chr10-84719603;