Variant 11-6259936-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_176875.4(CCKBR):c.8T>G(p.Leu3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000764 in 1,308,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

CCKBR
NM_176875.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCKBR	NM_176875.4 linkuse as main transcript	c.8T>G	p.Leu3Arg	missense_variant	1/5	ENST00000334619.7
CCKBR	NM_001363552.2 linkuse as main transcript	c.8T>G	p.Leu3Arg	missense_variant	1/4
CCKBR	NM_001318029.2 linkuse as main transcript	c.8T>G	p.Leu3Arg	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCKBR	ENST00000334619.7 linkuse as main transcript	c.8T>G	p.Leu3Arg	missense_variant	1/5	1	NM_176875.4	P1	P32239-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.64e-7

AC:

AN:

1308938

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

642368

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000614

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 13, 2021

The c.8T>G (p.L3R) alteration is located in exon 1 (coding exon 1) of the CCKBR gene. This alteration results from a T to G substitution at nucleotide position 8, causing the leucine (L) at amino acid position 3 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;.;.;.

Eigen

Benign

-0.0071

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Pathogenic

0.29

MetaRNN

Uncertain

0.52

D;D;D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.90

L;.;.;.;L

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.85

N;N;N;D;N

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D;D

Polyphen

1.0

D;.;.;.;D

Vest4

0.59

MutPred

0.22

Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);

MVP

0.88

MPC

0.61

ClinPred

0.50

GERP RS

0.18

Varity_R

0.32

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over