rs4836698

Positions:

• chr9-130219711-C-T

Variant summary

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

The NM_014286.4(NCS1):​c.229-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,614,058 control chromosomes in the GnomAD database, including 546 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 0.015 (62 hom., cov: 32)
  • Exomes 𝑓: 0.014 (484 hom.)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCS1	NM_014286.4	c.229-14C>T		intron_variant		ENST00000372398.6	NP_055101.2
NCS1	NM_001128826.2	c.175-14C>T		intron_variant			NP_001122298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6	c.229-14C>T		intron_variant		1	NM_014286.4	ENSP00000361475.3
NCS1	ENST00000630865.1	c.175-14C>T		intron_variant		3		ENSP00000486695.1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2329 AN: 152240 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0657

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00889

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.0267 AC: 6700 AN: 251328 Hom.: 347 AF XY: 0.0221 AC XY: 2997 AN XY: 135874

Gnomad AFR exome AF: 0.00320

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00696

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0128

Gnomad OTH exome AF: 0.0215

GnomAD4 exome AF: 0.0138 AC: 20174 AN: 1461700 Hom.: 484 Cov.: 32 AF XY: 0.0132 AC XY: 9611 AN XY: 727170

Gnomad4 AFR exome AF: 0.00260

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00654

Gnomad4 FIN exome AF: 0.0213

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0153 AC: 2327 AN: 152358 Hom.: 62 Cov.: 32 AF XY: 0.0159 AC XY: 1187 AN XY: 74496

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00869

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0167 Hom.: 9

Bravo AF: 0.0197

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.80

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: rs4836698; hg19: chr9-132981990;