NM_014286.4:c.229-14C>T

Variant names:

• chr9-130219711-C-T
• rs4836698
• NM_014286.4:c.229-14C>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.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
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0622 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.229-14C>T		intron	N/A	NP_055101.2
	NCS1	NM_001128826.2		c.175-14C>T		intron	N/A	NP_001122298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCS1	ENST00000372398.6	TSL:1 MANE Select	c.229-14C>T		intron	N/A	ENSP00000361475.3
	NCS1	ENST00000630865.1	TSL:3	c.175-14C>T		intron	N/A	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

GnomAD2 exomes AF: 0.0267 AC: 6700 AN: 251328 AF XY: 0.0221

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 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

African (AFR) AF: 0.00260 AC: 87 AN: 33476

American (AMR) AF: 0.116 AC: 5205 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 330 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00654 AC: 564 AN: 86256

European-Finnish (FIN) AF: 0.0213 AC: 1136 AN: 53412

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5764

European-Non Finnish (NFE) AF: 0.0109 AC: 12117 AN: 1111850

Other (OTH) AF: 0.0120 AC: 723 AN: 60392

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

African (AFR) AF: 0.00327 AC: 136 AN: 41588

American (AMR) AF: 0.0655 AC: 1003 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00869 AC: 42 AN: 4834

European-Finnish (FIN) AF: 0.0208 AC: 221 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 839 AN: 68030

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0166 Hom.: 9

Bravo AF: 0.0197

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.80
PhyloP100		0.20
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: rs4836698; hg19: chr9-132981990;