9-130237179-G-C

Position:

• chr9-130237179-G-C

Variant summary

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

The NM_014286.4(NCS1):​c.*4207G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,968 control chromosomes in the GnomAD database, including 17,666 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 0.48 (17656 hom., cov: 31)
  • Exomes 𝑓: 0.39 (10 hom.)
• Consequence: NCS1 NM_014286.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCS1	NM_014286.4	c.*4207G>C		3_prime_UTR_variant	8/8	ENST00000372398.6
NCS1	NM_001128826.2	c.*4207G>C		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCS1	ENST00000372398.6	c.*4207G>C		3_prime_UTR_variant	8/8	1	NM_014286.4	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72443 AN: 151728 Hom.: 17643 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.392 AC: 47 AN: 120 Hom.: 10 Cov.: 0 AF XY: 0.390 AC XY: 39 AN XY: 100

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.477 AC: 72503 AN: 151848 Hom.: 17656 Cov.: 31 AF XY: 0.472 AC XY: 35063 AN XY: 74218

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.483

Alfa AF: 0.321 Hom.: 729

Bravo AF: 0.469

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.81

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: rs1055663; hg19: chr9-132999458;