Genetic Variant CCK:c.-213-47G>A (chr3-42264954-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.-213-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,190 control chromosomes in the GnomAD database, including 20,587 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 0.52 ( 20544 hom., cov: 31)

Exomes 𝑓: 0.58 ( 43 hom. )

Consequence

CCK
NM_000729.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.194

Publications

11 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

new If you want to explore the variant's impact on the transcript NM_000729.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.75).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000729.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCK	NM_000729.6	MANE Select	c.-213-47G>A		intron	N/A	NP_000720.1	Q6FG82

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCK	ENST00000396169.7	TSL:1 MANE Select	c.-213-47G>A	intron	N/A	ENSP00000379472.2	P06307
ENSG00000281160	ENST00000631079.3	TSL:6	n.41C>T	non_coding_transcript_exon	Exon 1 of 1
CCK	ENST00000334681.9	TSL:1	c.-260G>A	upstream_gene	N/A	ENSP00000335657.5	P06307

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78678

AN:

151822

Hom.:

20531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.563

Gnomad SAS

AF:

0.633

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.541

GnomAD4 exome

AF:

0.576

AC:

144

AN:

250

Hom.:

Cov.:

AF XY:

0.576

AC XY:

114

AN XY:

198

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.375

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.552

AC:

117

AN:

212

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.518

AC:

78721

AN:

151940

Hom.:

20544

Cov.:

AF XY:

0.524

AC XY:

38932

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.525

AC:

21741

AN:

41426

American (AMR)

AF:

0.540

AC:

8252

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

2272

AN:

3470

East Asian (EAS)

AF:

0.563

AC:

2889

AN:

5134

South Asian (SAS)

AF:

0.632

AC:

3041

AN:

4810

European-Finnish (FIN)

AF:

0.543

AC:

5752

AN:

10584

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.484

AC:

32894

AN:

67932

Other (OTH)

AF:

0.542

AC:

1140

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1949

3898

5846

7795

9744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.499

Hom.:

44508

Bravo

AF:

0.514

Asia WGS

AF:

0.605

AC:

2104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.8

(source)

DANN

Benign

0.77

PhyloP100

0.19

PromoterAI

-0.095

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over