9-130186271-T-C

Position:

• chr9-130186271-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014286.4(NCS1):​c.64+13544T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,046 control chromosomes in the GnomAD database, including 38,412 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 0.70 (38412 hom., cov: 32)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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

Verdict is Benign. Variant got -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 = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCS1	NM_014286.4	c.64+13544T>C		intron_variant		ENST00000372398.6	NP_055101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6	c.64+13544T>C		intron_variant		1	NM_014286.4	ENSP00000361475	P1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106342 AN: 151928 Hom.: 38413 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.700 AC: 106371 AN: 152046 Hom.: 38412 Cov.: 32 AF XY: 0.708 AC XY: 52592 AN XY: 74322

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.693

Alfa AF: 0.744 Hom.: 38193

Bravo AF: 0.672

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs3824544; hg19: chr9-132948550;