9-130177513-G-C

Variant summary

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

The NM_014286.4(NCS1):c.64+4786G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,190 control chromosomes in the GnomAD database, including 2,875 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 0.17 (2875 hom., cov: 32)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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 = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCS1	NM_014286.4	c.64+4786G>C		intron_variant		ENST00000372398.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCS1	ENST00000372398.6	c.64+4786G>C		intron_variant		1	NM_014286.4	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25432 AN: 152070 Hom.: 2871 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.167 AC: 25461 AN: 152190 Hom.: 2875 Cov.: 32 AF XY: 0.174 AC XY: 12940 AN XY: 74404

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.173

Alfa AF: 0.0607 Hom.: 59

Bravo AF: 0.178

Asia WGS AF: 0.348 AC: 1210 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	0.0060
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

Other links and lift over

dbSNP: rs4836694; hg19: chr9-132939792;