3-42264954-C-T

Position:

• chr3-42264954-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.-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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]

ENSG00000281160 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCK	NM_000729.6	c.-213-47G>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.-213-47G>A		intron_variant		1	NM_000729.6	ENSP00000379472.2
ENSG00000281160	ENST00000631079.2	n.-31C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78678 AN: 151822 Hom.: 20531 Cov.: 31

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.: 43 Cov.: 0 AF XY: 0.576 AC XY: 114 AN XY: 198

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.518 AC: 78721 AN: 151940 Hom.: 20544 Cov.: 31 AF XY: 0.524 AC XY: 38932 AN XY: 74258

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.542

Alfa AF: 0.499 Hom.: 33601

Bravo AF: 0.514

Asia WGS AF: 0.605 AC: 2104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.8
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11571842; hg19: chr3-42306446; COSMIC: COSV58184519; COSMIC: COSV58184519;