rs504522

Variant summary

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

The ENST00000372141.7(NRG3):​c.1028-17573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,964 control chromosomes in the GnomAD database, including 15,960 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 ( 15960 hom., cov: 33)

Consequence

NRG3
ENST00000372141.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.529
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=-0.98).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NRG3NM_001010848.4 linkuse as main transcriptc.1028-17573C>T intron_variant ENST00000372141.7 NP_001010848.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NRG3ENST00000372141.7 linkuse as main transcriptc.1028-17573C>T intron_variant 1 NM_001010848.4 ENSP00000361214 A2P56975-4

Frequencies

GnomAD3 genomes
AF:
0.454
AC:
68923
AN:
151844
Hom.:
15951
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.478
Gnomad AMI
AF:
0.223
Gnomad AMR
AF:
0.381
Gnomad ASJ
AF:
0.495
Gnomad EAS
AF:
0.127
Gnomad SAS
AF:
0.454
Gnomad FIN
AF:
0.414
Gnomad MID
AF:
0.405
Gnomad NFE
AF:
0.488
Gnomad OTH
AF:
0.440
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.454
AC:
68960
AN:
151964
Hom.:
15960
Cov.:
33
AF XY:
0.447
AC XY:
33220
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.478
Gnomad4 AMR
AF:
0.381
Gnomad4 ASJ
AF:
0.495
Gnomad4 EAS
AF:
0.128
Gnomad4 SAS
AF:
0.454
Gnomad4 FIN
AF:
0.414
Gnomad4 NFE
AF:
0.488
Gnomad4 OTH
AF:
0.439
Alfa
AF:
0.447
Hom.:
2664
Bravo
AF:
0.448
Asia WGS
AF:
0.300
AC:
1047
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.33
DANN
Benign
0.43

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: rs504522; hg19: chr10-84607594; API