rs1336291

Variant names:

• chr10-82215622-C-T
• rs1336291
• NM_001010848.4:c.824-143117C>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.824-143117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,092 control chromosomes in the GnomAD database, including 912 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 0.11 (912 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 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.824-143117C>T		intron	N/A	NP_001010848.2	P56975-4
	NRG3	NM_001370084.1		c.824-143117C>T		intron	N/A	NP_001357013.1	D9ZHP6
	NRG3	NM_001370081.1		c.824-143117C>T		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.824-143117C>T		intron	N/A	ENSP00000361214.2	P56975-4
	NRG3	ENST00000404547.5	TSL:1	c.824-143117C>T		intron	N/A	ENSP00000384796.1	P56975-1
	NRG3	ENST00000556918.5	TSL:1	c.236-17120C>T		intron	N/A	ENSP00000451376.1	D9ZHQ7

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16043 AN: 151974 Hom.: 911 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00964

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.106 AC: 16055 AN: 152092 Hom.: 912 Cov.: 32 AF XY: 0.107 AC XY: 7975 AN XY: 74352

African (AFR) AF: 0.147 AC: 6105 AN: 41478

American (AMR) AF: 0.0961 AC: 1468 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3472

East Asian (EAS) AF: 0.00947 AC: 49 AN: 5174

South Asian (SAS) AF: 0.150 AC: 721 AN: 4810

European-Finnish (FIN) AF: 0.112 AC: 1187 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0853 AC: 5799 AN: 68004

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.0976 Hom.: 96

Bravo AF: 0.100

Asia WGS AF: 0.0630 AC: 220 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.15
DANN	Benign	0.72
PhyloP100		-1.8
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: rs1336291; hg19: chr10-83975378;