4-26489489-A-G

Variant names:

• chr4-26489489-A-G
• rs1800857
• NM_000730.3:c.113-5T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000730.3(CCKAR):​c.113-5T>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 0.155 in 1,611,920 control chromosomes in the GnomAD database, including 22,325 homozygotes. In-silico tool predicts a benign outcome for this variant. 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 0.18 (2638 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19687 hom.)
• Consequence: CCKAR NM_000730.3 splice_region, intron
• Scores: Splicing: ADA: 0.00005808
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCKAR	NM_000730.3	c.113-5T>C		splice_region_variant, intron_variant	Intron 1 of 4	ENST00000295589.4	NP_000721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCKAR	ENST00000295589.4	c.113-5T>C		splice_region_variant, intron_variant	Intron 1 of 4	1	NM_000730.3	ENSP00000295589.3

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

GnomAD2 exomes AF: 0.169 AC: 42004 AN: 248440 AF XY: 0.176

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 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

African (AFR) AF: 0.255 AC: 8523 AN: 33446

American (AMR) AF: 0.112 AC: 5002 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7450 AN: 26124

East Asian (EAS) AF: 0.287 AC: 11404 AN: 39668

South Asian (SAS) AF: 0.295 AC: 25449 AN: 86228

European-Finnish (FIN) AF: 0.0976 AC: 5205 AN: 53308

Middle Eastern (MID) AF: 0.207 AC: 1192 AN: 5762

European-Non Finnish (NFE) AF: 0.134 AC: 148346 AN: 1110304

Other (OTH) AF: 0.178 AC: 10751 AN: 60322

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

African (AFR) AF: 0.251 AC: 10418 AN: 41462

American (AMR) AF: 0.130 AC: 1980 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1195 AN: 5130

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4808

European-Finnish (FIN) AF: 0.0991 AC: 1050 AN: 10594

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9331 AN: 67980

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.162 Hom.: 1422

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
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800857; hg19: chr4-26491111; COSMIC: COSV55161156;