rs7873936

chr9-130230883-A-Gchr9-130230883-A-T

Variant summary

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

The NM_014286.4(NCS1):c.*18-2107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 151,520 control chromosomes in the GnomAD database, including 46,976 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 0.78 (46976 hom., cov: 28)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCS1	NM_014286.4	c.*18-2107A>G		intron_variant		ENST00000372398.6
NCS1	NM_001128826.2	c.*18-2107A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCS1	ENST00000372398.6	c.*18-2107A>G		intron_variant		1	NM_014286.4	P1
NCS1	ENST00000630865.1	c.*18-2107A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.784 AC: 118749 AN: 151402 Hom.: 46949 Cov.: 28

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.784 AC: 118819 AN: 151520 Hom.: 46976 Cov.: 28 AF XY: 0.788 AC XY: 58350 AN XY: 74030

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.776

Alfa AF: 0.811 Hom.: 59383

Bravo AF: 0.767

Asia WGS AF: 0.827 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	11
Dann	Benign	0.66

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: rs7873936; hg19: chr9-132993162;