Genetic Variant NCS1:c.*4207G>C (chr9-130237179-G-C) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

3 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=-0.76).

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 rank	MANE	Protein	UniProt
NCS1	NM_014286.4 link	c.*4207G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000372398.6	NP_055101.2	P62166-1A0A024R8B2
NCS1	NM_001128826.2 link	c.*4207G>C		3_prime_UTR_variant	Exon 8 of 8		NP_001122298.1	P62166-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCS1	ENST00000372398.6 link	c.*4207G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_014286.4	ENSP00000361475.3		P62166-1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72443

AN:

151728

Hom.:

17643

Cov.:

show subpopulations

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:

AN:

120

Hom.:

Cov.:

AF XY:

0.390

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.370

AC:

AN:

100

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.477

AC:

72503

AN:

151848

Hom.:

17656

Cov.:

AF XY:

0.472

AC XY:

35063

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.487

AC:

20166

AN:

41376

American (AMR)

AF:

0.391

AC:

5979

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1752

AN:

3472

East Asian (EAS)

AF:

0.229

AC:

1177

AN:

5142

South Asian (SAS)

AF:

0.516

AC:

2481

AN:

4808

European-Finnish (FIN)

AF:

0.457

AC:

4808

AN:

10512

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34316

AN:

67944

Other (OTH)

AF:

0.483

AC:

1022

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1897

3794

5692

7589

9486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.321

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

(source)

DANN

Benign

0.81

PhyloP100

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over