Genetic Variant NM_000729.6: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:

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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=-0.62).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCK	NM_000729.6	MANE Select	c.-108T>C		5_prime_UTR	Exon 3 of 5	NP_000720.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CCK	ENST00000396169.7	TSL:1 MANE Select	c.-108T>C	5_prime_UTR	Exon 3 of 5	ENSP00000379472.2
CCK	ENST00000334681.9	TSL:1	c.-108T>C	5_prime_UTR	Exon 1 of 3	ENSP00000335657.5
CCK	ENST00000484359.1	TSL:2	n.-37T>C	upstream_gene	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over