10-82114627-T-C

Variant names:

• chr10-82114627-T-C
• rs1896506
• NM_001010848.4:c.823+238464T>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.823+238464T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,084 control chromosomes in the GnomAD database, including 47,200 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 0.79 (47200 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 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.823+238464T>C		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.823+238464T>C		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.823+238464T>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.823+238464T>C		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.823+238464T>C		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.136-52100T>C		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119509 AN: 151964 Hom.: 47152 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.786 AC: 119612 AN: 152084 Hom.: 47200 Cov.: 32 AF XY: 0.792 AC XY: 58849 AN XY: 74336

African (AFR) AF: 0.779 AC: 32328 AN: 41502

American (AMR) AF: 0.844 AC: 12889 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2300 AN: 3472

East Asian (EAS) AF: 0.895 AC: 4592 AN: 5130

South Asian (SAS) AF: 0.856 AC: 4126 AN: 4822

European-Finnish (FIN) AF: 0.808 AC: 8558 AN: 10592

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52142 AN: 67970

Other (OTH) AF: 0.805 AC: 1701 AN: 2114

Alfa AF: 0.775 Hom.: 35194

Bravo AF: 0.788

Asia WGS AF: 0.861 AC: 2995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.28
PhyloP100		-1.5
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: rs1896506; hg19: chr10-83874383;