Genetic Variant CCK:c.215-147G>A (chr3-42258378-C-T) – 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.215-147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 790,576 control chromosomes in the GnomAD database, including 56,904 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 0.35 ( 9708 hom., cov: 32)

Exomes 𝑓: 0.38 ( 47196 hom. )

Consequence

CCK
NM_000729.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.539

Publications

9 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:

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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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCK	NM_000729.6 link	c.215-147G>A		intron_variant	Intron 4 of 4	ENST00000396169.7	NP_000720.1	P06307Q6FG82
CCK	NM_001174138.3 link	c.215-147G>A		intron_variant	Intron 2 of 2		NP_001167609.1	P06307Q6FG82

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCK	ENST00000396169.7 link	c.215-147G>A	intron_variant	Intron 4 of 4	1	NM_000729.6	ENSP00000379472.2	P06307
CCK	ENST00000334681.9 link	c.215-147G>A	intron_variant	Intron 2 of 2	1		ENSP00000335657.5	P06307
CCK	ENST00000434608.1 link	c.215-147G>A	intron_variant	Intron 2 of 2	1		ENSP00000409124.1	P06307

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53250

AN:

151922

Hom.:

9705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.385

GnomAD4 exome

AF:

0.382

AC:

244082

AN:

638536

Hom.:

47196

AF XY:

0.386

AC XY:

126522

AN XY:

327390

show subpopulations

African (AFR)

AF:

0.285

AC:

4453

AN:

15620

American (AMR)

AF:

0.341

AC:

5714

AN:

16744

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

7042

AN:

14610

East Asian (EAS)

AF:

0.512

AC:

16413

AN:

32060

South Asian (SAS)

AF:

0.476

AC:

21899

AN:

45994

European-Finnish (FIN)

AF:

0.310

AC:

10728

AN:

34604

Middle Eastern (MID)

AF:

0.396

AC:

1137

AN:

2872

European-Non Finnish (NFE)

AF:

0.370

AC:

164444

AN:

444072

Other (OTH)

AF:

0.383

AC:

12252

AN:

31960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

7090

14179

21269

28358

35448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3538

7076

10614

14152

17690

<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:

0.350

AC:

53273

AN:

152040

Hom.:

9708

Cov.:

AF XY:

0.352

AC XY:

26186

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.288

AC:

11930

AN:

41466

American (AMR)

AF:

0.362

AC:

5531

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1617

AN:

3470

East Asian (EAS)

AF:

0.526

AC:

2720

AN:

5172

South Asian (SAS)

AF:

0.500

AC:

2406

AN:

4816

European-Finnish (FIN)

AF:

0.310

AC:

3270

AN:

10556

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24418

AN:

67966

Other (OTH)

AF:

0.385

AC:

813

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1753

3506

5260

7013

8766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.367

Hom.:

13553

Bravo

AF:

0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.12

(source)

DANN

Benign

0.72

PhyloP100

-0.54

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