9-130182266-T-C

Variant names:

• chr9-130182266-T-C
• rs7849345
• NM_014286.4:c.64+9539T>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.64+9539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,892 control chromosomes in the GnomAD database, including 20,091 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 0.51 (20091 hom., cov: 31)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 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.64+9539T>C		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.64+9539T>C		intron	N/A	ENSP00000361475.3	P62166-1
	NCS1	ENST00000946320.1		c.64+9539T>C		intron	N/A	ENSP00000616379.1
	NCS1	ENST00000946321.1		c.64+9539T>C		intron	N/A	ENSP00000616380.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76979 AN: 151774 Hom.: 20067 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.507 AC: 77053 AN: 151892 Hom.: 20091 Cov.: 31 AF XY: 0.504 AC XY: 37429 AN XY: 74234

African (AFR) AF: 0.549 AC: 22765 AN: 41430

American (AMR) AF: 0.511 AC: 7809 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3470

East Asian (EAS) AF: 0.151 AC: 777 AN: 5142

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4808

European-Finnish (FIN) AF: 0.515 AC: 5433 AN: 10544

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34696 AN: 67914

Other (OTH) AF: 0.506 AC: 1069 AN: 2112

Alfa AF: 0.513 Hom.: 28918

Bravo AF: 0.512

Asia WGS AF: 0.309 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.54
PhyloP100		0.25
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: rs7849345; hg19: chr9-132944545;