10-82059369-T-G

Variant names:

• chr10-82059369-T-G
• rs4933824
• NM_001010848.4:c.823+183206T>G

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+183206T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,124 control chromosomes in the GnomAD database, including 62,195 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 0.90 (62195 hom., cov: 31)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.965 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+183206T>G		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.823+183206T>G		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.823+183206T>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+183206T>G		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.823+183206T>G		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.136-107358T>G		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136591 AN: 152006 Hom.: 62173 Cov.: 31

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.991

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.920

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

GnomAD4 genome AF: 0.898 AC: 136665 AN: 152124 Hom.: 62195 Cov.: 31 AF XY: 0.902 AC XY: 67078 AN XY: 74350

African (AFR) AF: 0.731 AC: 30283 AN: 41434

American (AMR) AF: 0.942 AC: 14408 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3384 AN: 3472

East Asian (EAS) AF: 0.924 AC: 4758 AN: 5150

South Asian (SAS) AF: 0.988 AC: 4767 AN: 4824

European-Finnish (FIN) AF: 0.991 AC: 10524 AN: 10616

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65492 AN: 68016

Other (OTH) AF: 0.921 AC: 1943 AN: 2110

Alfa AF: 0.940 Hom.: 203019

Bravo AF: 0.886

Asia WGS AF: 0.954 AC: 3317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.57
PhyloP100		-1.4
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: rs4933824; hg19: chr10-83819125;