rs1800857

chr4-26489489-A-Gchr4-26489489-A-T

Variant summary

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

The NM_000730.3(CCKAR):c.113-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,611,920 control chromosomes in the GnomAD database, including 22,325 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 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 0.18 (2638 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19687 hom.)
• Consequence: CCKAR NM_000730.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005808
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

Genes affected

CCKAR (HGNC:1570): (cholecystokinin A receptor) This gene encodes a G-protein coupled receptor that binds non-sulfated members of the cholecystokinin (CCK) family of peptide hormones. This receptor is a major physiologic mediator of pancreatic enzyme secretion and smooth muscle contraction of the gallbladder and stomach. In the central and peripheral nervous system this receptor regulates satiety and the release of beta-endorphin and dopamine. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCKAR	NM_000730.3	c.113-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000295589.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCKAR	ENST00000295589.4	c.113-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000730.3	P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26818 AN: 151930 Hom.: 2636 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.178

GnomAD3 exomes AF: 0.169 AC: 42004 AN: 248440 Hom.: 4163 AF XY: 0.176 AC XY: 23642 AN XY: 134452

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.296

Gnomad FIN exome AF: 0.0968

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.153 AC: 223322 AN: 1459872 Hom.: 19687 Cov.: 34 AF XY: 0.158 AC XY: 114447 AN XY: 726104

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.0976

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.177 AC: 26839 AN: 152048 Hom.: 2638 Cov.: 32 AF XY: 0.176 AC XY: 13106 AN XY: 74322

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.176

Alfa AF: 0.158 Hom.: 1028

Bravo AF: 0.179

Asia WGS AF: 0.244 AC: 848 AN: 3478

EpiCase AF: 0.154

EpiControl AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.34
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000058
dbscSNV1_RF	Benign	0.0020
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: rs1800857; hg19: chr4-26491111; COSMIC: COSV55161156;