9-130230883-A-G

Variant names:

• chr9-130230883-A-G
• rs7873936
• NM_014286.4:c.*18-2107A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014286.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCS1	NM_014286.4	MANE Select	c.*18-2107A>G		intron	N/A	NP_055101.2
	NCS1	NM_001128826.2		c.*18-2107A>G		intron	N/A	NP_001122298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCS1	ENST00000372398.6	TSL:1 MANE Select	c.*18-2107A>G		intron	N/A	ENSP00000361475.3
	NCS1	ENST00000630865.1	TSL:3	c.*18-2107A>G		intron	N/A	ENSP00000486695.1

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

African (AFR) AF: 0.680 AC: 27999 AN: 41200

American (AMR) AF: 0.758 AC: 11521 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3049 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4481 AN: 5172

South Asian (SAS) AF: 0.858 AC: 4111 AN: 4792

European-Finnish (FIN) AF: 0.901 AC: 9418 AN: 10452

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55510 AN: 67922

Other (OTH) AF: 0.776 AC: 1634 AN: 2106

Alfa AF: 0.801 Hom.: 92013

Bravo AF: 0.767

Asia WGS AF: 0.827 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.68
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: rs7873936; hg19: chr9-132993162;