rs947513

Positions:

• chr9-130211709-G-A
• chr9-130211709-G-C

Variant summary

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

The ENST00000372398.6(NCS1):​c.90-6123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,846 control chromosomes in the GnomAD database, including 22,440 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 0.54 (22440 hom., cov: 30)
• Consequence: NCS1 ENST00000372398.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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 = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCS1	NM_014286.4	c.90-6123G>A		intron_variant		ENST00000372398.6	NP_055101.2
NCS1	NM_001128826.2	c.36-6123G>A		intron_variant			NP_001122298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6	c.90-6123G>A		intron_variant		1	NM_014286.4	ENSP00000361475	P1
NCS1	ENST00000630865.1	c.36-6123G>A		intron_variant		3		ENSP00000486695
NCS1	ENST00000493042.1	n.144-6123G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81325 AN: 151728 Hom.: 22426 Cov.: 30

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.536 AC: 81371 AN: 151846 Hom.: 22440 Cov.: 30 AF XY: 0.544 AC XY: 40361 AN XY: 74180

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.519

Alfa AF: 0.531 Hom.: 21694

Bravo AF: 0.539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.75

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: rs947513; hg19: chr9-132973988;