10-81896144-T-C

Variant names:

• chr10-81896144-T-C
• rs10399981
• NM_001010848.4:c.823+19981T>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+19981T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 152,204 control chromosomes in the GnomAD database, including 264 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 0.053 (264 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• 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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.823+19981T>C		intron_variant	Intron 1 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.823+19981T>C		intron_variant	Intron 1 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8136 AN: 152086 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0535 AC: 8138 AN: 152204 Hom.: 264 Cov.: 32 AF XY: 0.0558 AC XY: 4151 AN XY: 74414

African (AFR) AF: 0.0219 AC: 911 AN: 41550

American (AMR) AF: 0.0507 AC: 774 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3468

East Asian (EAS) AF: 0.0591 AC: 306 AN: 5178

South Asian (SAS) AF: 0.156 AC: 749 AN: 4814

European-Finnish (FIN) AF: 0.0660 AC: 699 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0639 AC: 4345 AN: 68002

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0515 Hom.: 131

Bravo AF: 0.0485

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.19
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: rs10399981; hg19: chr10-83655900;