10-82858840-G-T

Variant names:

• chr10-82858840-G-T
• rs17685233
• NM_001010848.4:c.1028-6571G>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.1028-6571G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 152,172 control chromosomes in the GnomAD database, including 230 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 0.046 (230 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.067 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.1028-6571G>T		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.1028-6571G>T		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.1028-6574G>T		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.1028-6571G>T		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.1028-6571G>T		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.518-6571G>T		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7045 AN: 152062 Hom.: 230 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0478

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

GnomAD4 genome AF: 0.0463 AC: 7040 AN: 152172 Hom.: 230 Cov.: 32 AF XY: 0.0450 AC XY: 3349 AN XY: 74360

African (AFR) AF: 0.0154 AC: 641 AN: 41526

American (AMR) AF: 0.0304 AC: 464 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4814

European-Finnish (FIN) AF: 0.0585 AC: 619 AN: 10576

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0686 AC: 4666 AN: 68020

Other (OTH) AF: 0.0478 AC: 101 AN: 2114

Alfa AF: 0.0425 Hom.: 40

Bravo AF: 0.0420

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.78
PhyloP100		0.49
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: rs17685233; hg19: chr10-84618596;