10-82698835-C-T

Variant names:

• chr10-82698835-C-T
• rs994174
• NM_001010848.4:c.954-39742C>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.954-39742C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,034 control chromosomes in the GnomAD database, including 27,030 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 0.57 (27030 hom., cov: 33)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.954-39742C>T		intron_variant	Intron 2 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.954-39742C>T		intron_variant	Intron 2 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86301 AN: 151916 Hom.: 27023 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.568 AC: 86322 AN: 152034 Hom.: 27030 Cov.: 33 AF XY: 0.574 AC XY: 42625 AN XY: 74284

African (AFR) AF: 0.292 AC: 12125 AN: 41476

American (AMR) AF: 0.602 AC: 9177 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2021 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3432 AN: 5158

South Asian (SAS) AF: 0.636 AC: 3069 AN: 4826

European-Finnish (FIN) AF: 0.807 AC: 8535 AN: 10576

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46106 AN: 67970

Other (OTH) AF: 0.580 AC: 1219 AN: 2102

Alfa AF: 0.603 Hom.: 3852

Bravo AF: 0.541

Asia WGS AF: 0.647 AC: 2250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-0.13
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: rs994174; hg19: chr10-84458591;