4-26489495-A-T

Variant names:

• chr4-26489495-A-T
• rs1800855
• NM_000730.3:c.113-11T>A

Variant summary

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

The NM_000730.3(CCKAR):​c.113-11T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,610,626 control chromosomes in the GnomAD database, including 56,404 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 0.28 (6835 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49569 hom.)
• Consequence: CCKAR NM_000730.3 intron
• Scores: Splicing: ADA: 0.0003463
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.56
• Publications: 14 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000730.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCKAR	NM_000730.3	MANE Select	c.113-11T>A		intron	N/A	NP_000721.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCKAR	ENST00000295589.4	TSL:1 MANE Select	c.113-11T>A		intron	N/A	ENSP00000295589.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42854 AN: 151836 Hom.: 6813 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.275 AC: 68182 AN: 248044 AF XY: 0.279

Gnomad AFR exome AF: 0.396

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.556

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.245 AC: 357985 AN: 1458672 Hom.: 49569 Cov.: 35 AF XY: 0.250 AC XY: 181661 AN XY: 725384

African (AFR) AF: 0.397 AC: 13257 AN: 33418

American (AMR) AF: 0.191 AC: 8525 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 9507 AN: 26116

East Asian (EAS) AF: 0.579 AC: 22969 AN: 39644

South Asian (SAS) AF: 0.409 AC: 35215 AN: 86186

European-Finnish (FIN) AF: 0.176 AC: 9376 AN: 53256

Middle Eastern (MID) AF: 0.292 AC: 1679 AN: 5756

European-Non Finnish (NFE) AF: 0.217 AC: 240461 AN: 1109336

Other (OTH) AF: 0.282 AC: 16996 AN: 60260

GnomAD4 genome AF: 0.283 AC: 42932 AN: 151954 Hom.: 6835 Cov.: 32 AF XY: 0.285 AC XY: 21154 AN XY: 74284

African (AFR) AF: 0.393 AC: 16286 AN: 41408

American (AMR) AF: 0.203 AC: 3095 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2888 AN: 5136

South Asian (SAS) AF: 0.430 AC: 2062 AN: 4794

European-Finnish (FIN) AF: 0.178 AC: 1880 AN: 10572

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14664 AN: 67984

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.253 Hom.: 984

Bravo AF: 0.286

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.33
PhyloP100		-5.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00035
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.19		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: rs1800855; hg19: chr4-26491117; COSMIC: COSV55163252;