rs3822222

chr4-26489030-G-A

Variant summary

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

The NM_000730.3(CCKAR):c.364+203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,114 control chromosomes in the GnomAD database, including 1,785 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 0.15 (1785 hom., cov: 32)
• Consequence: CCKAR NM_000730.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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 = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCKAR	NM_000730.3	c.364+203C>T		intron_variant		ENST00000295589.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCKAR	ENST00000295589.4	c.364+203C>T		intron_variant		1	NM_000730.3	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22393 AN: 151996 Hom.: 1784 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.147 AC: 22399 AN: 152114 Hom.: 1785 Cov.: 32 AF XY: 0.148 AC XY: 11023 AN XY: 74372

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.158

Alfa AF: 0.145 Hom.: 365

Bravo AF: 0.144

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.36
Dann	Benign	0.77

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: rs3822222; hg19: chr4-26490652; COSMIC: COSV55161176;