NM_014286.4:c.64+5001C>T

Variant names:

• chr9-130177728-C-T
• rs4837479
• NM_014286.4:c.64+5001C>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.64+5001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,156 control chromosomes in the GnomAD database, including 11,740 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 0.34 (11740 hom., cov: 33)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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.64+5001C>T		intron	N/A	NP_055101.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCS1	ENST00000372398.6	TSL:1 MANE Select	c.64+5001C>T		intron	N/A	ENSP00000361475.3
	NCS1	ENST00000946320.1		c.64+5001C>T		intron	N/A	ENSP00000616379.1
	NCS1	ENST00000946321.1		c.64+5001C>T		intron	N/A	ENSP00000616380.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51383 AN: 152038 Hom.: 11698 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.338 AC: 51486 AN: 152156 Hom.: 11740 Cov.: 33 AF XY: 0.342 AC XY: 25412 AN XY: 74392

African (AFR) AF: 0.605 AC: 25096 AN: 41488

American (AMR) AF: 0.394 AC: 6019 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3430 AN: 5160

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4816

European-Finnish (FIN) AF: 0.230 AC: 2438 AN: 10600

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12101 AN: 68004

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.230 Hom.: 21852

Bravo AF: 0.370

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.62
PhyloP100		-0.77
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: rs4837479; hg19: chr9-132940007;