rs504522

Positions:

• chr10-82847838-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000372141.7(NRG3):​c.1028-17573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,964 control chromosomes in the GnomAD database, including 15,960 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 0.45 (15960 hom., cov: 33)
• Consequence: NRG3 ENST00000372141.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1028-17573C>T		intron_variant		ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.1028-17573C>T		intron_variant		1	NM_001010848.4	ENSP00000361214	A2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68923 AN: 151844 Hom.: 15951 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.454 AC: 68960 AN: 151964 Hom.: 15960 Cov.: 33 AF XY: 0.447 AC XY: 33220 AN XY: 74264

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.439

Alfa AF: 0.447 Hom.: 2664

Bravo AF: 0.448

Asia WGS AF: 0.300 AC: 1047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs504522; hg19: chr10-84607594;