9-130196026-C-T

Variant summary

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

The NM_014286.4(NCS1):​c.65-4932C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,980 control chromosomes in the GnomAD database, including 43,112 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 0.72 ( 43112 hom., cov: 30)

Consequence

NCS1
NM_014286.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.19
Variant links:
Genes affected
NCS1 (HGNC:3953): (neuronal calcium sensor 1) This gene is a member of the neuronal calcium sensor gene family, which encode calcium-binding proteins expressed predominantly in neurons. The protein encoded by this gene regulates G protein-coupled receptor phosphorylation in a calcium-dependent manner and can substitute for calmodulin. The protein is associated with secretory granules and modulates synaptic transmission and synaptic plasticity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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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=-0.95).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NCS1NM_014286.4 linkuse as main transcriptc.65-4932C>T intron_variant ENST00000372398.6 NP_055101.2 P62166-1A0A024R8B2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NCS1ENST00000372398.6 linkuse as main transcriptc.65-4932C>T intron_variant 1 NM_014286.4 ENSP00000361475.3 P62166-1
NCS1ENST00000493042.1 linkuse as main transcriptn.118+2081C>T intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.724
AC:
110008
AN:
151862
Hom.:
43109
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.395
Gnomad AMI
AF:
0.854
Gnomad AMR
AF:
0.789
Gnomad ASJ
AF:
0.870
Gnomad EAS
AF:
0.951
Gnomad SAS
AF:
0.874
Gnomad FIN
AF:
0.881
Gnomad MID
AF:
0.766
Gnomad NFE
AF:
0.847
Gnomad OTH
AF:
0.757
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.724
AC:
110024
AN:
151980
Hom.:
43112
Cov.:
30
AF XY:
0.730
AC XY:
54216
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.394
Gnomad4 AMR
AF:
0.789
Gnomad4 ASJ
AF:
0.870
Gnomad4 EAS
AF:
0.951
Gnomad4 SAS
AF:
0.874
Gnomad4 FIN
AF:
0.881
Gnomad4 NFE
AF:
0.847
Gnomad4 OTH
AF:
0.759
Alfa
AF:
0.826
Hom.:
53352
Bravo
AF:
0.701
Asia WGS
AF:
0.870
AC:
3023
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.20
DANN
Benign
0.50

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: rs1342043; hg19: chr9-132958305; API