Genetic Variant CCKBR:c.404-10C>T (chr11-6270078-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_176875.4(CCKBR):c.404-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCKBR
NM_176875.4 intron

Scores

Splicing: ADA: 0.0001556

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCKBR	NM_176875.4 link	c.404-10C>T	intron_variant	Intron 2 of 4	ENST00000334619.7	NP_795344.1	P32239-1
CCKBR	NM_001363552.2 link	c.404-10C>T	intron_variant	Intron 2 of 3		NP_001350481.1
CCKBR	NM_001318029.2 link	c.152-10C>T	intron_variant	Intron 1 of 3		NP_001304958.1	P32239E9PIC8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCKBR	ENST00000334619.7 link	c.404-10C>T	intron_variant	Intron 2 of 4	1	NM_176875.4	ENSP00000335544.2	P32239-1
CCKBR	ENST00000525462.1 link	c.404-10C>T	intron_variant	Intron 2 of 3	1		ENSP00000435534.1	P32239-2
CCKBR	ENST00000525014.1 link	c.*150C>T	3_prime_UTR_variant	Exon 2 of 2	4		ENSP00000437001.1	E9PPL7
CCKBR	ENST00000532715.5 link	c.152-10C>T	intron_variant	Intron 1 of 3	3		ENSP00000432079.1	E9PIC8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444840

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715934

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000360

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.4

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.014

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over