rs17559044

Positions:

• chr10-82112793-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001010848.4(NRG3):​c.823+236630T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 152,174 control chromosomes in the GnomAD database, including 127 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 0.034 (127 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956

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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0338 (5141/152174) while in subpopulation NFE AF= 0.0491 (3341/68000). AF 95% confidence interval is 0.0477. There are 127 homozygotes in gnomad4. There are 2442 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 127 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.823+236630T>C		intron_variant		ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.823+236630T>C		intron_variant		1	NM_001010848.4	ENSP00000361214	A2

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5142 AN: 152056 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.00898

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0316

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

GnomAD4 genome AF: 0.0338 AC: 5141 AN: 152174 Hom.: 127 Cov.: 32 AF XY: 0.0328 AC XY: 2442 AN XY: 74398

Gnomad4 AFR AF: 0.00896

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0125

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.0491

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0363 Hom.: 12

Bravo AF: 0.0322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.51

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: rs17559044; hg19: chr10-83872549;