NM_001010848.4:c.1584-781T>C

Variant names:

• chr10-82984317-T-C
• rs1124013
• NM_001010848.4:c.1584-781T>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.1584-781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,014 control chromosomes in the GnomAD database, including 23,681 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 0.55 (23681 hom., cov: 32)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 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.1584-781T>C		intron	N/A	NP_001010848.2
	NRG3	NM_001370084.1		c.1584-466T>C		intron	N/A	NP_001357013.1
	NRG3	NM_001370081.1		c.1584-781T>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.1584-781T>C		intron	N/A	ENSP00000361214.2
	NRG3	ENST00000404547.5	TSL:1	c.1584-466T>C		intron	N/A	ENSP00000384796.1
	NRG3	ENST00000556918.5	TSL:1	c.1074-781T>C		intron	N/A	ENSP00000451376.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83524 AN: 151896 Hom.: 23663 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.550 AC: 83585 AN: 152014 Hom.: 23681 Cov.: 32 AF XY: 0.540 AC XY: 40118 AN XY: 74312

African (AFR) AF: 0.459 AC: 19008 AN: 41446

American (AMR) AF: 0.558 AC: 8516 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2205 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5168

South Asian (SAS) AF: 0.485 AC: 2340 AN: 4824

European-Finnish (FIN) AF: 0.470 AC: 4961 AN: 10548

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43133 AN: 67970

Other (OTH) AF: 0.579 AC: 1222 AN: 2110

Alfa AF: 0.586 Hom.: 3266

Bravo AF: 0.553

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.027
DANN	Benign	0.43
PhyloP100		-1.9
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: rs1124013; hg19: chr10-84744073;