rs947513

Variant names:

• chr9-130211709-G-A
• rs947513
• NM_014286.4:c.90-6123G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014286.4(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 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NCS1	NM_014286.4	c.90-6123G>A		intron_variant	Intron 2 of 7	ENST00000372398.6	NP_055101.2
NCS1	NM_001128826.2	c.36-6123G>A		intron_variant	Intron 2 of 7		NP_001122298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6	c.90-6123G>A		intron_variant	Intron 2 of 7	1	NM_014286.4	ENSP00000361475.3
NCS1	ENST00000630865.1	c.36-6123G>A		intron_variant	Intron 2 of 7	3		ENSP00000486695.1
NCS1	ENST00000493042.1	n.144-6123G>A		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.459 AC: 19015 AN: 41398

American (AMR) AF: 0.479 AC: 7312 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1877 AN: 3470

East Asian (EAS) AF: 0.844 AC: 4313 AN: 5110

South Asian (SAS) AF: 0.714 AC: 3441 AN: 4816

European-Finnish (FIN) AF: 0.663 AC: 6971 AN: 10514

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.539 AC: 36627 AN: 67958

Other (OTH) AF: 0.519 AC: 1097 AN: 2112

Alfa AF: 0.528 Hom.: 28991

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
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs947513; hg19: chr9-132973988;