3-42264472-C-T

Position:

• chr3-42264472-C-T

Variant summary

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

The NM_000729.6(CCK):​c.-3+225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,136 control chromosomes in the GnomAD database, including 4,445 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 0.21 (4445 hom., cov: 32)
• Consequence: CCK NM_000729.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCK	NM_000729.6	c.-3+225G>A		intron_variant		ENST00000396169.7	NP_000720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCK	ENST00000396169.7	c.-3+225G>A		intron_variant		1	NM_000729.6	ENSP00000379472.2
CCK	ENST00000334681.9	c.-3+225G>A		intron_variant		1		ENSP00000335657.5
CCK	ENST00000484359.1	n.69+225G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31669 AN: 152018 Hom.: 4444 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31666 AN: 152136 Hom.: 4445 Cov.: 32 AF XY: 0.220 AC XY: 16347 AN XY: 74366

Gnomad4 AFR AF: 0.0509

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.200

Alfa AF: 0.226 Hom.: 2890

Bravo AF: 0.187

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.69

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: rs747455; hg19: chr3-42305964;