NM_001010848.4:c.1413-293C>T

Variant names:

• chr10-82978657-C-T
• rs3818306
• NM_001010848.4:c.1413-293C>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.1413-293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,944 control chromosomes in the GnomAD database, including 12,073 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 (12073 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 6 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 = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1413-293C>T		intron_variant	Intron 7 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.1413-293C>T		intron_variant	Intron 7 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58318 AN: 151826 Hom.: 12071 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.384 AC: 58340 AN: 151944 Hom.: 12073 Cov.: 32 AF XY: 0.378 AC XY: 28093 AN XY: 74264

African (AFR) AF: 0.250 AC: 10345 AN: 41444

American (AMR) AF: 0.375 AC: 5729 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1082 AN: 5152

South Asian (SAS) AF: 0.305 AC: 1464 AN: 4802

European-Finnish (FIN) AF: 0.381 AC: 4021 AN: 10542

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

European-Non Finnish (NFE) AF: 0.480 AC: 32617 AN: 67958

Other (OTH) AF: 0.429 AC: 906 AN: 2114

Alfa AF: 0.427 Hom.: 9671

Bravo AF: 0.380

Asia WGS AF: 0.278 AC: 964 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	0.81
DANN	Benign	0.22
PhyloP100		-0.68
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: rs3818306; hg19: chr10-84738413;