NM_000730.3:c.365-469T>C

Variant names:

• chr4-26486367-A-G
• rs2000978
• NM_000730.3:c.365-469T>C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.00983

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.125

Alfa AF: 0.132 Hom.: 754

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

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: rs2000978; hg19: chr4-26487989;