chr9-130193174-C-T

Position:

• chr9-130193174-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014286.4(NCS1):​c.65-7784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,054 control chromosomes in the GnomAD database, including 28,561 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 0.59 (28561 hom., cov: 33)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCS1	NM_014286.4	c.65-7784C>T		intron_variant		ENST00000372398.6	NP_055101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6	c.65-7784C>T		intron_variant		1	NM_014286.4	ENSP00000361475	P1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88957 AN: 151936 Hom.: 28562 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.585 AC: 88961 AN: 152054 Hom.: 28561 Cov.: 33 AF XY: 0.595 AC XY: 44243 AN XY: 74338

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.579

Alfa AF: 0.661 Hom.: 33926

Bravo AF: 0.549

Asia WGS AF: 0.748 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs10819611; hg19: chr9-132955453;