3-42263639-C-G

Variant names:

• chr3-42263639-C-G
• rs754635
• NM_000729.6:c.-2-7G>C

Variant summary

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

The NM_000729.6(CCK):​c.-2-7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 1,555,678 control chromosomes in the GnomAD database, including 587,738 homozygotes. 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 0.82 (51712 hom., cov: 35)
  • Exomes 𝑓: 0.87 (536026 hom.)
• Consequence: CCK NM_000729.6 splice_region, intron
• Scores: Splicing: ADA: 0.00002282
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• 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 rank	MANE	Protein	UniProt
CCK	NM_000729.6	c.-2-7G>C		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000396169.7	NP_000720.1
CCK	NM_001174138.3	c.-2-7G>C		splice_region_variant, intron_variant	Intron 1 of 2		NP_001167609.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124453 AN: 152180 Hom.: 51697 Cov.: 35

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.842

GnomAD3 exomes AF: 0.838 AC: 150564 AN: 179756 Hom.: 63659 AF XY: 0.846 AC XY: 82799 AN XY: 97890

Gnomad AFR exome AF: 0.668

Gnomad AMR exome AF: 0.727

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.709

Gnomad SAS exome AF: 0.866

Gnomad FIN exome AF: 0.913

Gnomad NFE exome AF: 0.885

Gnomad OTH exome AF: 0.867

GnomAD4 exome AF: 0.872 AC: 1224097 AN: 1403380 Hom.: 536026 Cov.: 61 AF XY: 0.874 AC XY: 604823 AN XY: 692406

Gnomad4 AFR exome AF: 0.670

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.943

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.865

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.886

Gnomad4 OTH exome AF: 0.869

GnomAD4 genome AF: 0.818 AC: 124516 AN: 152298 Hom.: 51712 Cov.: 35 AF XY: 0.819 AC XY: 61003 AN XY: 74486

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.839

Alfa AF: 0.860 Hom.: 10005

Bravo AF: 0.798

Asia WGS AF: 0.778 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.010
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: rs754635; hg19: chr3-42305131;