Genetic Variant CCK:c.-108T>C (chr3-42264802-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000729.6(CCK):c.-108T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,246 control chromosomes in the GnomAD database, including 52,052 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 0.82 ( 52001 hom., cov: 31)

Exomes 𝑓: 0.81 ( 51 hom. )

Consequence

CCK
NM_000729.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0140

Publications

24 publications found

Variant links:

Genes affected

CCK (HGNC:1569): (cholecystokinin) This gene encodes a member of the gastrin/cholecystokinin family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the peptide hormones cholecystokinin-8, -12, -33, and others. The encoded peptides have been shown to regulate gastric acid secretion and food intake. A sulfated form of cholecystokinin-8 may modulate neuronal activity in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

CCK links:

ENSG00000281160 (HGNC:):

ENSG00000281160 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=-0.62).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCK	NM_000729.6 link	c.-108T>C		5_prime_UTR_variant	Exon 3 of 5	ENST00000396169.7	NP_000720.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CCK	ENST00000396169.7 link	c.-108T>C	5_prime_UTR_variant	Exon 3 of 5	1	NM_000729.6	ENSP00000379472.2
CCK	ENST00000334681.9 link	c.-108T>C	5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000335657.5
CCK	ENST00000484359.1 link	n.-37T>C	upstream_gene_variant		2
ENSG00000281160	ENST00000631079.3 link	n.-112A>G	upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.821

AC:

124807

AN:

151974

Hom.:

51986

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.934

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.937

Gnomad EAS

AF:

0.711

Gnomad SAS

AF:

0.863

Gnomad FIN

AF:

0.915

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.889

Gnomad OTH

AF:

0.845

GnomAD4 exome

AF:

0.805

AC:

124

AN:

154

Hom.:

Cov.:

AF XY:

0.777

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.625

AC:

AN:

American (AMR)

AF:

0.667

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

0.625

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.917

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.815

AC:

AN:

108

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.821

AC:

124872

AN:

152092

Hom.:

52001

Cov.:

AF XY:

0.823

AC XY:

61164

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.685

AC:

28389

AN:

41444

American (AMR)

AF:

0.810

AC:

12388

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.937

AC:

3254

AN:

3472

East Asian (EAS)

AF:

0.710

AC:

3647

AN:

5134

South Asian (SAS)

AF:

0.864

AC:

4164

AN:

4822

European-Finnish (FIN)

AF:

0.915

AC:

9711

AN:

10612

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.889

AC:

60436

AN:

68008

Other (OTH)

AF:

0.842

AC:

1775

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1098

2196

3295

4393

5491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.860

Hom.:

73340

Bravo

AF:

0.801

Asia WGS

AF:

0.780

AC:

2715

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

0.014

PromoterAI

0.14

Neutral

(source)

Mutation Taster

=300/0

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