NM_014286.4:c.89+3935A>G

Variant names:

• chr9-130204917-A-G
• rs7024495
• NM_014286.4:c.89+3935A>G

Variant summary

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

The NM_014286.4(NCS1):​c.89+3935A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,552 control chromosomes in the GnomAD database, including 19,168 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 0.49 (19168 hom., cov: 29)
• Consequence: NCS1 NM_014286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCS1	NM_014286.4	c.89+3935A>G		intron_variant	Intron 2 of 7	ENST00000372398.6	NP_055101.2
NCS1	NM_001128826.2	c.35+3935A>G		intron_variant	Intron 2 of 7		NP_001122298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6	c.89+3935A>G		intron_variant	Intron 2 of 7	1	NM_014286.4	ENSP00000361475.3
NCS1	ENST00000630865.1	c.35+3935A>G		intron_variant	Intron 2 of 7	3		ENSP00000486695.1
NCS1	ENST00000493042.1	n.143+3935A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74623 AN: 151432 Hom.: 19160 Cov.: 29

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.493 AC: 74654 AN: 151552 Hom.: 19168 Cov.: 29 AF XY: 0.502 AC XY: 37205 AN XY: 74048

African (AFR) AF: 0.405 AC: 16725 AN: 41292

American (AMR) AF: 0.447 AC: 6809 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1851 AN: 3466

East Asian (EAS) AF: 0.853 AC: 4366 AN: 5116

South Asian (SAS) AF: 0.709 AC: 3377 AN: 4762

European-Finnish (FIN) AF: 0.610 AC: 6417 AN: 10526

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33413 AN: 67854

Other (OTH) AF: 0.484 AC: 1019 AN: 2106

Alfa AF: 0.494 Hom.: 74153

Bravo AF: 0.474

Asia WGS AF: 0.721 AC: 2504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-1.0
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: rs7024495; hg19: chr9-132967196;