rs1764072

Variant names:

• chr10-82204740-A-G
• rs1764072
• NM_001010848.4:c.824-153999A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010848.4(NRG3):​c.824-153999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,106 control chromosomes in the GnomAD database, including 2,689 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 (2689 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.824-153999A>G		intron_variant	Intron 1 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.824-153999A>G		intron_variant	Intron 1 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26114 AN: 151986 Hom.: 2680 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.172 AC: 26145 AN: 152106 Hom.: 2689 Cov.: 32 AF XY: 0.176 AC XY: 13055 AN XY: 74352

African (AFR) AF: 0.208 AC: 8631 AN: 41494

American (AMR) AF: 0.253 AC: 3863 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2010 AN: 5162

South Asian (SAS) AF: 0.327 AC: 1579 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1239 AN: 10582

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7933 AN: 67990

Other (OTH) AF: 0.158 AC: 334 AN: 2110

Alfa AF: 0.147 Hom.: 1597

Bravo AF: 0.181

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.024
DANN	Benign	0.76
PhyloP100		-1.4
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: rs1764072; hg19: chr10-83964496;