chr9-130226430-T-G

Variant names:

• chr9-130226430-T-G
• rs2277200
• NM_014286.4:c.516T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014286.4(NCS1):​c.516T>G​(p.Gly172Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,612,954 control chromosomes in the GnomAD database, including 89,139 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 0.36 (10122 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79017 hom.)
• Consequence: NCS1 NM_014286.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 19 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCS1	NM_014286.4	c.516T>G	p.Gly172Gly	synonymous_variant	Exon 7 of 8	ENST00000372398.6	NP_055101.2
NCS1	NM_001128826.2	c.462T>G	p.Gly154Gly	synonymous_variant	Exon 7 of 8		NP_001122298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6	c.516T>G	p.Gly172Gly	synonymous_variant	Exon 7 of 8	1	NM_014286.4	ENSP00000361475.3
NCS1	ENST00000630865.1	c.462T>G	p.Gly154Gly	synonymous_variant	Exon 7 of 8	3		ENSP00000486695.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53977 AN: 151732 Hom.: 10095 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.374

GnomAD2 exomes AF: 0.329 AC: 82493 AN: 250692 AF XY: 0.314

Gnomad AFR exome AF: 0.444

Gnomad AMR exome AF: 0.524

Gnomad ASJ exome AF: 0.359

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.323 AC: 471662 AN: 1461104 Hom.: 79017 Cov.: 37 AF XY: 0.318 AC XY: 231377 AN XY: 726846

African (AFR) AF: 0.447 AC: 14955 AN: 33466

American (AMR) AF: 0.512 AC: 22859 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 9203 AN: 26124

East Asian (EAS) AF: 0.184 AC: 7300 AN: 39684

South Asian (SAS) AF: 0.198 AC: 17095 AN: 86220

European-Finnish (FIN) AF: 0.249 AC: 13288 AN: 53366

Middle Eastern (MID) AF: 0.288 AC: 1661 AN: 5762

European-Non Finnish (NFE) AF: 0.329 AC: 365864 AN: 1111446

Other (OTH) AF: 0.322 AC: 19437 AN: 60366

GnomAD4 genome AF: 0.356 AC: 54048 AN: 151850 Hom.: 10122 Cov.: 32 AF XY: 0.347 AC XY: 25762 AN XY: 74186

African (AFR) AF: 0.445 AC: 18442 AN: 41410

American (AMR) AF: 0.417 AC: 6363 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3462

East Asian (EAS) AF: 0.168 AC: 862 AN: 5136

South Asian (SAS) AF: 0.198 AC: 948 AN: 4792

European-Finnish (FIN) AF: 0.228 AC: 2408 AN: 10540

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22683 AN: 67928

Other (OTH) AF: 0.371 AC: 782 AN: 2110

Alfa AF: 0.337 Hom.: 26406

Bravo AF: 0.377

Asia WGS AF: 0.230 AC: 798 AN: 3478

EpiCase AF: 0.325

EpiControl AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs2277200; hg19: chr9-132988709; COSMIC: COSV64962259;