chr9-130196026-C-T

Variant names:

• chr9-130196026-C-T
• rs1342043
• NM_014286.4:c.65-4932C>T

Variant summary

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

The NM_014286.4(NCS1):​c.65-4932C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,980 control chromosomes in the GnomAD database, including 43,112 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 0.72 (43112 hom., cov: 30)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCS1	NM_014286.4	MANE Select	c.65-4932C>T		intron	N/A	NP_055101.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCS1	ENST00000372398.6	TSL:1 MANE Select	c.65-4932C>T		intron	N/A	ENSP00000361475.3	P62166-1
	NCS1	ENST00000946320.1		c.65-4932C>T		intron	N/A	ENSP00000616379.1
	NCS1	ENST00000946321.1		c.65-4932C>T		intron	N/A	ENSP00000616380.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110008 AN: 151862 Hom.: 43109 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.724 AC: 110024 AN: 151980 Hom.: 43112 Cov.: 30 AF XY: 0.730 AC XY: 54216 AN XY: 74280

African (AFR) AF: 0.394 AC: 16305 AN: 41386

American (AMR) AF: 0.789 AC: 12057 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3014 AN: 3466

East Asian (EAS) AF: 0.951 AC: 4898 AN: 5150

South Asian (SAS) AF: 0.874 AC: 4203 AN: 4810

European-Finnish (FIN) AF: 0.881 AC: 9330 AN: 10592

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57612 AN: 67984

Other (OTH) AF: 0.759 AC: 1601 AN: 2110

Alfa AF: 0.822 Hom.: 61830

Bravo AF: 0.701

Asia WGS AF: 0.870 AC: 3023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-2.2
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: rs1342043; hg19: chr9-132958305;