Variant 11-6260037-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_176875.4(CCKBR):c.109C>T(p.Leu37Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,598,122 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 8 hom. )

Consequence

CCKBR
NM_176875.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.418

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046909153).

BP6

Variant 11-6260037-C-T is Benign according to our data. Variant chr11-6260037-C-T is described in ClinVar as [Benign]. Clinvar id is 723129.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000439 (635/1445960) while in subpopulation EAS AF= 0.0164 (622/37906). AF 95% confidence interval is 0.0153. There are 8 homozygotes in gnomad4_exome. There are 318 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCKBR	NM_176875.4 linkuse as main transcript	c.109C>T	p.Leu37Phe	missense_variant	1/5	ENST00000334619.7
CCKBR	NM_001363552.2 linkuse as main transcript	c.109C>T	p.Leu37Phe	missense_variant	1/4
CCKBR	NM_001318029.2 linkuse as main transcript	c.109C>T	p.Leu37Phe	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCKBR	ENST00000334619.7 linkuse as main transcript	c.109C>T	p.Leu37Phe	missense_variant	1/5	1	NM_176875.4	P1	P32239-1

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00989

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000452

AC:

103

AN:

228104

Hom.:

AF XY:

0.000470

AC XY:

AN XY:

125612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00631

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.000439

AC:

635

AN:

1445960

Hom.:

Cov.:

AF XY:

0.000442

AC XY:

318

AN XY:

719354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000335

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00991

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.000291

ExAC

AF:

0.000553

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

T;.;.;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.83

T;T;T;T;T

MetaRNN

Benign

0.0047

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.81

L;.;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.24

N;N;N;D;N

REVEL

Benign

0.089

Sift

Benign

0.16

T;D;T;D;T

Sift4G

Benign

0.14

T;D;T;D;T

Polyphen

0.20

B;.;.;.;B

Vest4

0.039

MVP

0.78

MPC

0.37

ClinPred

0.042

GERP RS

1.9

Varity_R

0.086

gMVP

0.30

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