Genetic Variant NM_014286.4:c.*517G>A (chr9-130233489-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014286.4(NCS1):c.*517G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,356 control chromosomes in the GnomAD database, including 16,379 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 0.45 ( 16304 hom., cov: 31)

Exomes 𝑓: 0.59 ( 75 hom. )

Consequence

NCS1
NM_014286.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

17 publications found

Variant links:

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]

NCS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 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.*517G>A		3_prime_UTR	Exon 8 of 8	NP_055101.2
	NCS1	NM_001128826.2		c.*517G>A		3_prime_UTR	Exon 8 of 8	NP_001122298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCS1	ENST00000372398.6	TSL:1 MANE Select	c.*517G>A		3_prime_UTR	Exon 8 of 8	ENSP00000361475.3
	NCS1	ENST00000630865.1	TSL:3	c.*517G>A		downstream_gene	N/A	ENSP00000486695.1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68202

AN:

151814

Hom.:

16303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.658

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.486

GnomAD4 exome

AF:

0.595

AC:

251

AN:

422

Hom.:

Cov.:

AF XY:

0.577

AC XY:

143

AN XY:

248

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.594

AC:

246

AN:

414

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.449

AC:

68234

AN:

151934

Hom.:

16304

Cov.:

AF XY:

0.454

AC XY:

33717

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.310

AC:

12851

AN:

41446

American (AMR)

AF:

0.435

AC:

6637

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.658

AC:

2283

AN:

3468

East Asian (EAS)

AF:

0.197

AC:

1017

AN:

5150

South Asian (SAS)

AF:

0.604

AC:

2916

AN:

4824

European-Finnish (FIN)

AF:

0.585

AC:

6172

AN:

10556

Middle Eastern (MID)

AF:

0.582

AC:

170

AN:

292

European-Non Finnish (NFE)

AF:

0.511

AC:

34706

AN:

67910

Other (OTH)

AF:

0.487

AC:

1026

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1795

3590

5384

7179

8974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.476

Hom.:

31296

Bravo

AF:

0.426

Asia WGS

AF:

0.417

AC:

1448

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.0

(source)

DANN

Benign

0.72

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over