9-130193174-C-T

Variant names:

• chr9-130193174-C-T
• rs10819611
• NM_014286.4:c.65-7784C>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.65-7784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,054 control chromosomes in the GnomAD database, including 28,561 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 0.59 (28561 hom., cov: 33)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 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.65-7784C>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.65-7784C>T		intron	N/A	ENSP00000361475.3	P62166-1
	NCS1	ENST00000946320.1		c.65-7784C>T		intron	N/A	ENSP00000616379.1
	NCS1	ENST00000946321.1		c.65-7784C>T		intron	N/A	ENSP00000616380.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88957 AN: 151936 Hom.: 28562 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.585 AC: 88961 AN: 152054 Hom.: 28561 Cov.: 33 AF XY: 0.595 AC XY: 44243 AN XY: 74338

African (AFR) AF: 0.319 AC: 13207 AN: 41456

American (AMR) AF: 0.545 AC: 8330 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3472

East Asian (EAS) AF: 0.853 AC: 4386 AN: 5142

South Asian (SAS) AF: 0.764 AC: 3688 AN: 4830

European-Finnish (FIN) AF: 0.823 AC: 8712 AN: 10588

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46312 AN: 67970

Other (OTH) AF: 0.579 AC: 1220 AN: 2108

Alfa AF: 0.645 Hom.: 42731

Bravo AF: 0.549

Asia WGS AF: 0.748 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.71
PhyloP100		-1.3
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: rs10819611; hg19: chr9-132955453;