rs7069578

Variant names:

• chr10-82420131-G-A
• rs7069578
• NM_001010848.4:c.953+61263G>A

Variant summary

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

The NM_001010848.4(NRG3):​c.953+61263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,966 control chromosomes in the GnomAD database, including 5,756 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 0.22 (5756 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.953+61263G>A		intron_variant	Intron 2 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.953+61263G>A		intron_variant	Intron 2 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33951 AN: 151848 Hom.: 5735 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.224 AC: 34032 AN: 151966 Hom.: 5756 Cov.: 32 AF XY: 0.221 AC XY: 16415 AN XY: 74270

African (AFR) AF: 0.475 AC: 19668 AN: 41412

American (AMR) AF: 0.144 AC: 2194 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1046 AN: 5150

South Asian (SAS) AF: 0.113 AC: 541 AN: 4806

European-Finnish (FIN) AF: 0.167 AC: 1770 AN: 10582

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7941 AN: 67968

Other (OTH) AF: 0.174 AC: 367 AN: 2114

Alfa AF: 0.151 Hom.: 8051

Bravo AF: 0.232

Asia WGS AF: 0.191 AC: 665 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.80
PhyloP100		0.048
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7069578; hg19: chr10-84179887;