rs2224109

Variant names:

• chr10-81974389-A-G
• rs2224109
• NM_001010848.4:c.823+98226A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-81974389-A-G
• chr10-81974389-A-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+98226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,964 control chromosomes in the GnomAD database, including 20,237 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 (20237 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 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.823+98226A>G		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.823+98226A>G		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.823+98226A>G		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.823+98226A>G		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.823+98226A>G		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.135+96294A>G		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69729 AN: 151846 Hom.: 20175 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.460 AC: 69849 AN: 151964 Hom.: 20237 Cov.: 32 AF XY: 0.465 AC XY: 34567 AN XY: 74278

African (AFR) AF: 0.785 AC: 32538 AN: 41452

American (AMR) AF: 0.515 AC: 7851 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1156 AN: 3466

East Asian (EAS) AF: 0.770 AC: 3966 AN: 5152

South Asian (SAS) AF: 0.439 AC: 2114 AN: 4816

European-Finnish (FIN) AF: 0.336 AC: 3556 AN: 10576

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17406 AN: 67930

Other (OTH) AF: 0.424 AC: 895 AN: 2112

Alfa AF: 0.382 Hom.: 6066

Bravo AF: 0.493

Asia WGS AF: 0.599 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.25
PhyloP100		-0.50
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: rs2224109; hg19: chr10-83734145;