rs6584400

Variant names:

• chr10-81896770-G-A
• rs6584400
• NM_001010848.4:c.823+20607G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-81896770-G-A
• chr10-81896770-G-C
• chr10-81896770-G-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.823+20607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,586 control chromosomes in the GnomAD database, including 4,829 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 (4829 hom., cov: 31)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 15 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.823+20607G>A		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.823+20607G>A		intron_variant	Intron 1 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33281 AN: 151472 Hom.: 4812 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.220 AC: 33339 AN: 151586 Hom.: 4829 Cov.: 31 AF XY: 0.219 AC XY: 16199 AN XY: 74052

African (AFR) AF: 0.419 AC: 17271 AN: 41252

American (AMR) AF: 0.142 AC: 2166 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3466

East Asian (EAS) AF: 0.246 AC: 1257 AN: 5116

South Asian (SAS) AF: 0.230 AC: 1106 AN: 4810

European-Finnish (FIN) AF: 0.133 AC: 1391 AN: 10464

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9008 AN: 67948

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.154 Hom.: 9863

Bravo AF: 0.227

Asia WGS AF: 0.231 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.64
PhyloP100		-0.96
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: rs6584400; hg19: chr10-83656526;