Genetic Variant CCK:c.-2-7G>A (chr3-42263639-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000729.6(CCK):c.-2-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCK
NM_000729.6 splice_region, intron

Scores

Splicing: ADA: 0.00006456

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.288

Publications

20 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCK	ENST00000396169.7 link	c.-2-7G>A	splice_region_variant, intron_variant	Intron 3 of 4	1	NM_000729.6	ENSP00000379472.2	P06307
CCK	ENST00000334681.9 link	c.-2-7G>A	splice_region_variant, intron_variant	Intron 1 of 2	1		ENSP00000335657.5	P06307
CCK	ENST00000434608.1 link	c.-2-7G>A	splice_region_variant, intron_variant	Intron 1 of 2	1		ENSP00000409124.1	P06307
CCK	ENST00000484359.1 link	n.70-7G>A	splice_region_variant, intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152196

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1403604

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692524

African (AFR)

AF:

0.00

AC:

AN:

31954

American (AMR)

AF:

0.00

AC:

AN:

35542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23542

East Asian (EAS)

AF:

0.00

AC:

AN:

37944

South Asian (SAS)

AF:

0.00

AC:

AN:

78772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4880

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083002

Other (OTH)

AF:

0.00

AC:

AN:

57748

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2090

Alfa

AF:

0.00

Hom.:

10005

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.3

(source)

DANN

Benign

0.95

PhyloP100

-0.29

PromoterAI

-0.017

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.0020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over