rs11196700

Variant names:

• chr10-82974984-G-A
• rs11196700
• NM_001010848.4:c.1412+1069G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010848.4(NRG3):​c.1412+1069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,036 control chromosomes in the GnomAD database, including 16,605 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 0.45 (16605 hom., cov: 33)
• Consequence: NRG3 NM_001010848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.909
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.1412+1069G>A		intron_variant	Intron 7 of 8	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.1412+1069G>A		intron_variant	Intron 7 of 8	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67856 AN: 151918 Hom.: 16604 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.446 AC: 67878 AN: 152036 Hom.: 16605 Cov.: 33 AF XY: 0.440 AC XY: 32689 AN XY: 74294

African (AFR) AF: 0.265 AC: 10985 AN: 41480

American (AMR) AF: 0.417 AC: 6361 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2015 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1170 AN: 5160

South Asian (SAS) AF: 0.407 AC: 1965 AN: 4824

European-Finnish (FIN) AF: 0.451 AC: 4762 AN: 10552

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

European-Non Finnish (NFE) AF: 0.572 AC: 38890 AN: 67964

Other (OTH) AF: 0.485 AC: 1023 AN: 2110

Alfa AF: 0.490 Hom.: 2476

Bravo AF: 0.436

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.58
PhyloP100		-0.91
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: rs11196700; hg19: chr10-84734740;