4-26486367-A-G

Variant names:

• chr4-26486367-A-G
• rs2000978
• NM_000730.3:c.365-469T>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.365-469T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,282 control chromosomes in the GnomAD database, including 1,343 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 0.12 (1343 hom., cov: 32)
• Consequence: CCKAR NM_000730.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCKAR	NM_000730.3	c.365-469T>C		intron_variant	Intron 2 of 4	ENST00000295589.4	NP_000721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCKAR	ENST00000295589.4	c.365-469T>C		intron_variant	Intron 2 of 4	1	NM_000730.3	ENSP00000295589.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18206 AN: 152164 Hom.: 1342 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18207 AN: 152282 Hom.: 1343 Cov.: 32 AF XY: 0.116 AC XY: 8634 AN XY: 74468

African (AFR) AF: 0.0495 AC: 2057 AN: 41574

American (AMR) AF: 0.124 AC: 1895 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3468

East Asian (EAS) AF: 0.00983 AC: 51 AN: 5190

South Asian (SAS) AF: 0.119 AC: 574 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1392 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11326 AN: 68004

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.142 Hom.: 3249

Bravo AF: 0.118

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		0.067
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2000978; hg19: chr4-26487989;