3-42258378-C-T

Position:

• chr3-42258378-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.215-147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 790,576 control chromosomes in the GnomAD database, including 56,904 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 0.35 (9708 hom., cov: 32)
  • Exomes 𝑓: 0.38 (47196 hom.)
• Consequence: CCK NM_000729.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCK	NM_000729.6	c.215-147G>A		intron_variant		ENST00000396169.7	NP_000720.1
CCK	NM_001174138.3	c.215-147G>A		intron_variant			NP_001167609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCK	ENST00000396169.7	c.215-147G>A		intron_variant		1	NM_000729.6	ENSP00000379472.2
CCK	ENST00000334681.9	c.215-147G>A		intron_variant		1		ENSP00000335657.5
CCK	ENST00000434608.1	c.215-147G>A		intron_variant		1		ENSP00000409124.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53250 AN: 151922 Hom.: 9705 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.382 AC: 244082 AN: 638536 Hom.: 47196 AF XY: 0.386 AC XY: 126522 AN XY: 327390

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.350 AC: 53273 AN: 152040 Hom.: 9708 Cov.: 32 AF XY: 0.352 AC XY: 26186 AN XY: 74300

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.385

Alfa AF: 0.367 Hom.: 9849

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.72

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: rs8192472; hg19: chr3-42299870;