chr9-130211709-G-C

Variant names:

• chr9-130211709-G-C
• rs947513
• NM_014286.4:c.90-6123G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014286.4(NCS1):​c.90-6123G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 151,908 control chromosomes in the GnomAD database, including 373 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 0.039 (373 hom., cov: 30)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 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.90-6123G>C		intron	N/A	NP_055101.2
	NCS1	NM_001128826.2		c.36-6123G>C		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.90-6123G>C		intron	N/A	ENSP00000361475.3
	NCS1	ENST00000630865.1	TSL:3	c.36-6123G>C		intron	N/A	ENSP00000486695.1
	NCS1	ENST00000493042.1	TSL:3	n.144-6123G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5866 AN: 151790 Hom.: 373 Cov.: 30

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000665

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0387 AC: 5876 AN: 151908 Hom.: 373 Cov.: 30 AF XY: 0.0363 AC XY: 2694 AN XY: 74210

African (AFR) AF: 0.131 AC: 5415 AN: 41416

American (AMR) AF: 0.0222 AC: 339 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.000665 AC: 7 AN: 10522

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000780 AC: 53 AN: 67978

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.00000491 Hom.: 28991

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.71
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: rs947513; hg19: chr9-132973988;