rs1474

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001010848.4(NRG3):​c.824-143853C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,078 control chromosomes in the GnomAD database, including 22,549 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 0.51 ( 22549 hom., cov: 32)

Consequence

NRG3
NM_001010848.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.991
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NRG3NM_001010848.4 linkuse as main transcriptc.824-143853C>G intron_variant ENST00000372141.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NRG3ENST00000372141.7 linkuse as main transcriptc.824-143853C>G intron_variant 1 NM_001010848.4 A2P56975-4

Frequencies

GnomAD3 genomes
AF:
0.511
AC:
77689
AN:
151960
Hom.:
22495
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.792
Gnomad AMI
AF:
0.571
Gnomad AMR
AF:
0.500
Gnomad ASJ
AF:
0.291
Gnomad EAS
AF:
0.610
Gnomad SAS
AF:
0.508
Gnomad FIN
AF:
0.358
Gnomad MID
AF:
0.465
Gnomad NFE
AF:
0.370
Gnomad OTH
AF:
0.496
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.512
AC:
77799
AN:
152078
Hom.:
22549
Cov.:
32
AF XY:
0.509
AC XY:
37876
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.793
Gnomad4 AMR
AF:
0.500
Gnomad4 ASJ
AF:
0.291
Gnomad4 EAS
AF:
0.609
Gnomad4 SAS
AF:
0.507
Gnomad4 FIN
AF:
0.358
Gnomad4 NFE
AF:
0.370
Gnomad4 OTH
AF:
0.500
Alfa
AF:
0.424
Hom.:
1892
Bravo
AF:
0.533
Asia WGS
AF:
0.570
AC:
1982
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
0.24
DANN
Benign
0.39

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1474; hg19: chr10-83974642; API