rs682284

Variant names:

• chr10-82570657-G-A
• rs682284
• NM_001010848.4:c.954-167920G>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.954-167920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 151,550 control chromosomes in the GnomAD database, including 598 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 0.079 (598 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010848.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	NM_001010848.4	MANE Select	c.954-167920G>A		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.954-167920G>A		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.954-167920G>A		intron	N/A	NP_001357010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	ENST00000372141.7	TSL:1 MANE Select	c.954-167920G>A		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.954-167920G>A		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.444-167920G>A		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11924 AN: 151432 Hom.: 598 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0787 AC: 11925 AN: 151550 Hom.: 598 Cov.: 32 AF XY: 0.0788 AC XY: 5836 AN XY: 74052

African (AFR) AF: 0.0197 AC: 815 AN: 41466

American (AMR) AF: 0.0644 AC: 976 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 207 AN: 3456

East Asian (EAS) AF: 0.148 AC: 757 AN: 5128

South Asian (SAS) AF: 0.106 AC: 510 AN: 4814

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10564

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7325 AN: 67650

Other (OTH) AF: 0.0790 AC: 166 AN: 2102

Alfa AF: 0.0591 Hom.: 83

Bravo AF: 0.0738

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.83
PhyloP100		0.069
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: rs682284; hg19: chr10-84330413;