rs2207768

Positions:

• chr10-82042647-C-T

Variant summary

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

The NM_001010848.4(NRG3):​c.823+166484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,798 control chromosomes in the GnomAD database, including 32,324 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 0.64 (32324 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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]

LOC124902472 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.823+166484C>T		intron_variant		ENST00000372141.7	NP_001010848.2
LOC124902472	XR_007062219.1	n.18608C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.823+166484C>T		intron_variant		1	NM_001010848.4	ENSP00000361214	A2

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96590 AN: 151680 Hom.: 32312 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.637 AC: 96632 AN: 151798 Hom.: 32324 Cov.: 32 AF XY: 0.641 AC XY: 47574 AN XY: 74174

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.666

Alfa AF: 0.703 Hom.: 72546

Bravo AF: 0.621

Asia WGS AF: 0.824 AC: 2861 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.57

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: rs2207768; hg19: chr10-83802403;