rs7919853

Variant names:

• chr10-82797197-C-T
• rs7919853
• NM_001010848.4:c.1027+58547C>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.1027+58547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,138 control chromosomes in the GnomAD database, including 2,188 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 0.17 (2188 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1027+58547C>T		intron_variant	Intron 3 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.1027+58547C>T		intron_variant	Intron 3 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25556 AN: 152020 Hom.: 2183 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.168 AC: 25572 AN: 152138 Hom.: 2188 Cov.: 32 AF XY: 0.168 AC XY: 12471 AN XY: 74374

African (AFR) AF: 0.160 AC: 6651 AN: 41518

American (AMR) AF: 0.148 AC: 2263 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3470

East Asian (EAS) AF: 0.0501 AC: 259 AN: 5174

South Asian (SAS) AF: 0.259 AC: 1246 AN: 4816

European-Finnish (FIN) AF: 0.125 AC: 1321 AN: 10598

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12419 AN: 67966

Other (OTH) AF: 0.161 AC: 341 AN: 2114

Alfa AF: 0.188 Hom.: 1661

Bravo AF: 0.166

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		2.0
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: rs7919853; hg19: chr10-84556953;