rs2207782

Variant names:

• chr10-81997443-G-A
• rs2207782
• NM_001010848.4:c.823+121280G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-81997443-G-A
• chr10-81997443-G-C

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+121280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,088 control chromosomes in the GnomAD database, including 20,158 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 0.46 (20158 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	NM_001010848.4	MANE Select	c.823+121280G>A		intron	N/A	NP_001010848.2	P56975-4
	NRG3	NM_001370084.1		c.823+121280G>A		intron	N/A	NP_001357013.1	D9ZHP6
	NRG3	NM_001370081.1		c.823+121280G>A		intron	N/A	NP_001357010.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG3	ENST00000372141.7	TSL:1 MANE Select	c.823+121280G>A		intron	N/A	ENSP00000361214.2	P56975-4
	NRG3	ENST00000404547.5	TSL:1	c.823+121280G>A		intron	N/A	ENSP00000384796.1	P56975-1
	NRG3	ENST00000556918.5	TSL:1	c.135+119348G>A		intron	N/A	ENSP00000451376.1	D9ZHQ7

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69558 AN: 151970 Hom.: 20102 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.458 AC: 69672 AN: 152088 Hom.: 20158 Cov.: 32 AF XY: 0.464 AC XY: 34466 AN XY: 74340

African (AFR) AF: 0.783 AC: 32508 AN: 41520

American (AMR) AF: 0.513 AC: 7838 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3468

East Asian (EAS) AF: 0.767 AC: 3956 AN: 5158

South Asian (SAS) AF: 0.435 AC: 2102 AN: 4830

European-Finnish (FIN) AF: 0.336 AC: 3549 AN: 10558

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17304 AN: 67962

Other (OTH) AF: 0.423 AC: 892 AN: 2108

Alfa AF: 0.405 Hom.: 15939

Bravo AF: 0.491

Asia WGS AF: 0.600 AC: 2087 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.62
PhyloP100		-0.74
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: rs2207782; hg19: chr10-83757199;