Variant chr11-6270078-C-G 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.404-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,597,178 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 69 hom. )

Consequence

CCKBR
NM_176875.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008538

Clinical Significance

Benign criteria provided, single submitter B:1

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-6270078-C-G is Benign according to our data. Variant chr11-6270078-C-G is described in ClinVar as [Benign]. Clinvar id is 769794.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00217 (331/152344) while in subpopulation AMR AF= 0.0189 (290/15308). AF 95% confidence interval is 0.0172. There are 3 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CCKBR	NM_176875.4 linkuse as main transcript	c.404-10C>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000334619.7
CCKBR	NM_001318029.2 linkuse as main transcript	c.152-10C>G	splice_polypyrimidine_tract_variant, intron_variant
CCKBR	NM_001363552.2 linkuse as main transcript	c.404-10C>G	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCKBR	ENST00000334619.7 linkuse as main transcript	c.404-10C>G	splice_polypyrimidine_tract_variant, intron_variant		1	NM_176875.4	P1	P32239-1
CCKBR	ENST00000525462.1 linkuse as main transcript	c.404-10C>G	splice_polypyrimidine_tract_variant, intron_variant		1			P32239-2
CCKBR	ENST00000525014.1 linkuse as main transcript	c.*150C>G	3_prime_UTR_variant	2/2	4
CCKBR	ENST00000532715.5 linkuse as main transcript	c.152-10C>G	splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

334

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0192

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:

0.00191

GnomAD3 exomes

AF:

0.00805

AC:

1935

AN:

240498

Hom.:

AF XY:

0.00579

AC XY:

754

AN XY:

130188

show subpopulations

Gnomad AFR exome

AF:

0.000442

Gnomad AMR exome

AF:

0.0556

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00646

GnomAD4 exome

AF:

0.00159

AC:

2292

AN:

1444834

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

907

AN XY:

715930

show subpopulations

Gnomad4 AFR exome

AF:

0.000452

Gnomad4 AMR exome

AF:

0.0498

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:

0.0000227

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00217

AC:

331

AN:

152344

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.0189

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:

0.00189

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.00483

Asia WGS

AF:

0.000866

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.2

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00085

dbscSNV1_RF

Benign

0.17

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