3-42264802-A-G

Position:

• chr3-42264802-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CCK	NM_000729.6	c.-108T>C		5_prime_UTR_variant	3/5	ENST00000396169.7	NP_000720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCK	ENST00000396169.7	c.-108T>C		5_prime_UTR_variant	3/5	1	NM_000729.6	ENSP00000379472.2
CCK	ENST00000334681.9	c.-108T>C		5_prime_UTR_variant	1/3	1		ENSP00000335657.5
CCK	ENST00000484359.1	n.-37T>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124807 AN: 151974 Hom.: 51986 Cov.: 31

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.: 51 Cov.: 0 AF XY: 0.777 AC XY: 73 AN XY: 94

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.821 AC: 124872 AN: 152092 Hom.: 52001 Cov.: 31 AF XY: 0.823 AC XY: 61164 AN XY: 74348

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.842

Alfa AF: 0.869 Hom.: 56972

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	13
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs1799923; hg19: chr3-42306294;