10-82688071-T-C

Variant names:

• chr10-82688071-T-C
• rs2250544
• NM_001010848.4:c.954-50506T>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.954-50506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 152,242 control chromosomes in the GnomAD database, including 64,032 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 0.92 (64032 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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]

ENSG00000300011 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.954-50506T>C		intron	N/A	NP_001010848.2	P56975-4
	NRG3	NM_001370084.1		c.954-50506T>C		intron	N/A	NP_001357013.1	D9ZHP6
	NRG3	NM_001370081.1		c.954-50506T>C		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.954-50506T>C		intron	N/A	ENSP00000361214.2	P56975-4
	NRG3	ENST00000404547.5	TSL:1	c.954-50506T>C		intron	N/A	ENSP00000384796.1	P56975-1
	NRG3	ENST00000556918.5	TSL:1	c.444-50506T>C		intron	N/A	ENSP00000451376.1	D9ZHQ7

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139464 AN: 152124 Hom.: 63986 Cov.: 32

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.917 AC: 139567 AN: 152242 Hom.: 64032 Cov.: 32 AF XY: 0.918 AC XY: 68302 AN XY: 74432

African (AFR) AF: 0.916 AC: 38073 AN: 41548

American (AMR) AF: 0.920 AC: 14062 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 3001 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5165 AN: 5170

South Asian (SAS) AF: 0.927 AC: 4466 AN: 4820

European-Finnish (FIN) AF: 0.941 AC: 9974 AN: 10598

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61858 AN: 68022

Other (OTH) AF: 0.912 AC: 1928 AN: 2114

Alfa AF: 0.911 Hom.: 35049

Bravo AF: 0.917

Asia WGS AF: 0.961 AC: 3343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.50
PhyloP100		-1.2
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: rs2250544; hg19: chr10-84447827;