rs4837479

Positions:

• chr9-130177728-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.64+5001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,156 control chromosomes in the GnomAD database, including 11,740 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 0.34 (11740 hom., cov: 33)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCS1	NM_014286.4	c.64+5001C>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.64+5001C>T		intron_variant		1	NM_014286.4	ENSP00000361475.3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51383 AN: 152038 Hom.: 11698 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.338 AC: 51486 AN: 152156 Hom.: 11740 Cov.: 33 AF XY: 0.342 AC XY: 25412 AN XY: 74392

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.322

Alfa AF: 0.205 Hom.: 7296

Bravo AF: 0.370

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.62

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: rs4837479; hg19: chr9-132940007;