Variant 11-6260004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_176875.4(CCKBR):c.76G>A(p.Ala26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,588,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

CCKBR
NM_176875.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Variant links:

Genes affected

CCKBR (HGNC:1571): (cholecystokinin B receptor) This gene encodes a G-protein coupled receptor for gastrin and cholecystokinin (CCK), regulatory peptides of the brain and gastrointestinal tract. This protein is a type B gastrin receptor, which has a high affinity for both sulfated and nonsulfated CCK analogs and is found principally in the central nervous system and the gastrointestinal tract. Alternative splicing results in multiple transcript variants. A misspliced transcript variant including an intron has been observed in cells from colorectal and pancreatic tumors. [provided by RefSeq, Dec 2015]

CCKBR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09157789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCKBR	NM_176875.4 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	1/5	ENST00000334619.7
CCKBR	NM_001363552.2 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	1/4
CCKBR	NM_001318029.2 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCKBR	ENST00000334619.7 linkuse as main transcript	c.76G>A	p.Ala26Thr	missense_variant	1/5	1	NM_176875.4	P1	P32239-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000184

AC:

AN:

216844

Hom.:

AF XY:

0.0000333

AC XY:

AN XY:

120198

show subpopulations

Gnomad AFR exome

AF:

0.0000836

Gnomad AMR exome

AF:

0.0000329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000354

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1436666

Hom.:

Cov.:

AF XY:

0.0000336

AC XY:

AN XY:

714550

show subpopulations

Gnomad4 AFR exome

AF:

0.000128

Gnomad4 AMR exome

AF:

0.0000480

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000717

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000436

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2023

The c.76G>A (p.A26T) alteration is located in exon 1 (coding exon 1) of the CCKBR gene. This alteration results from a G to A substitution at nucleotide position 76, causing the alanine (A) at amino acid position 26 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.057

T;.;.;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.092

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.090

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.23

T;T;T;D;T

Sift4G

Benign

0.27

T;T;T;D;T

Polyphen

0.0060

B;.;.;.;B

Vest4

0.072

MutPred

0.14

Gain of glycosylation at A26 (P = 0.0234);Gain of glycosylation at A26 (P = 0.0234);Gain of glycosylation at A26 (P = 0.0234);Gain of glycosylation at A26 (P = 0.0234);Gain of glycosylation at A26 (P = 0.0234);

MVP

0.79

MPC

0.33

ClinPred

0.034

GERP RS

2.6

Varity_R

0.063

gMVP

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over