11-6271011-G-T

Position:

chr11-6271011-G-T

Variant summary

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

The NM_176875.4(CCKBR):c.812G>T(p.Gly271Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CCKBR
NM_176875.4 missense, splice_region

Scores

Splicing: ADA: 0.1469

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

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:

CCKBR (HGNC:):

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=0.14264867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCKBR	NM_176875.4 linkuse as main transcript	c.812G>T	p.Gly271Val	missense_variant, splice_region_variant	5/5	ENST00000334619.7	NP_795344.1	P32239-1
CCKBR	NM_001363552.2 linkuse as main transcript	c.1019G>T	p.Gly340Val	missense_variant	4/4		NP_001350481.1
CCKBR	NM_001318029.2 linkuse as main transcript	c.560G>T	p.Gly187Val	missense_variant, splice_region_variant	4/4		NP_001304958.1	P32239E9PIC8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCKBR	ENST00000525462.1 linkuse as main transcript	c.1019G>T	p.Gly340Val	missense_variant	4/4	1		ENSP00000435534.1	P32239-2
CCKBR	ENST00000334619.7 linkuse as main transcript	c.812G>T	p.Gly271Val	missense_variant, splice_region_variant	5/5	1	NM_176875.4	ENSP00000335544.2	P32239-1
CCKBR	ENST00000532396.1 linkuse as main transcript	n.44G>T		splice_region_variant, non_coding_transcript_exon_variant	2/2	1
CCKBR	ENST00000532715.5 linkuse as main transcript	c.560G>T	p.Gly187Val	missense_variant, splice_region_variant	4/4	3		ENSP00000432079.1	E9PIC8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250600

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

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

Jul 02, 2024

The c.812G>T (p.G271V) alteration is located in exon 5 (coding exon 5) of the CCKBR gene. This alteration results from a G to T substitution at nucleotide position 812, causing the glycine (G) at amino acid position 271 to be replaced by a valine (V). 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

0.087

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.58

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.4

M;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;D;T

Sift4G

Uncertain

0.054

T;T;T

Polyphen

0.49

P;.;P

Vest4

0.16

MutPred

0.52

Gain of sheet (P = 0.0221);.;.;

MVP

0.89

MPC

0.43

ClinPred

0.072

GERP RS

1.6

Varity_R

0.065

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.15

dbscSNV1_RF

Benign

0.44

SpliceAI score (max)

0.050

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