chr10-82705406-T-C

Variant names:

• chr10-82705406-T-C
• rs2494028
• NM_001010848.4:c.954-33171T>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.954-33171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,204 control chromosomes in the GnomAD database, including 62,567 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 0.91 (62567 hom., cov: 33)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 2 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 = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.954-33171T>C		intron_variant	Intron 2 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.954-33171T>C		intron_variant	Intron 2 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137813 AN: 152086 Hom.: 62529 Cov.: 33

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.906 AC: 137908 AN: 152204 Hom.: 62567 Cov.: 33 AF XY: 0.908 AC XY: 67543 AN XY: 74416

African (AFR) AF: 0.880 AC: 36531 AN: 41514

American (AMR) AF: 0.915 AC: 13977 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2995 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5148 AN: 5168

South Asian (SAS) AF: 0.927 AC: 4472 AN: 4824

European-Finnish (FIN) AF: 0.941 AC: 9990 AN: 10618

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.909 AC: 61845 AN: 68012

Other (OTH) AF: 0.906 AC: 1913 AN: 2112

Alfa AF: 0.909 Hom.: 105020

Bravo AF: 0.905

Asia WGS AF: 0.956 AC: 3327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.85
PhyloP100		0.28
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: rs2494028; hg19: chr10-84465162;