11-6271607-C-G

Position:

• chr11-6271607-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176875.4(CCKBR):​c.*64C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,449,788 control chromosomes in the GnomAD database, including 521,234 homozygotes. 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: 𝑓 0.80 (49707 hom., cov: 32)
  • Exomes 𝑓: 0.85 (471527 hom.)
• Consequence: CCKBR NM_176875.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCKBR	NM_176875.4	c.*64C>G		3_prime_UTR_variant	5/5	ENST00000334619.7	NP_795344.1
CCKBR	NM_001363552.2	c.*64C>G		3_prime_UTR_variant	4/4		NP_001350481.1
CCKBR	NM_001318029.2	c.*64C>G		3_prime_UTR_variant	4/4		NP_001304958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCKBR	ENST00000334619.7	c.*64C>G		3_prime_UTR_variant	5/5	1	NM_176875.4	ENSP00000335544.2
CCKBR	ENST00000525462.1	c.*64C>G		3_prime_UTR_variant	4/4	1		ENSP00000435534.1
CCKBR	ENST00000532715.5	c.*64C>G		3_prime_UTR_variant	4/4	3		ENSP00000432079.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122008 AN: 151714 Hom.: 49678 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.819

GnomAD4 exome AF: 0.851 AC: 1105121 AN: 1297956 Hom.: 471527 Cov.: 20 AF XY: 0.851 AC XY: 541945 AN XY: 636526

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.887

Gnomad4 ASJ exome AF: 0.872

Gnomad4 EAS exome AF: 0.942

Gnomad4 SAS exome AF: 0.838

Gnomad4 FIN exome AF: 0.895

Gnomad4 NFE exome AF: 0.851

Gnomad4 OTH exome AF: 0.852

GnomAD4 genome AF: 0.804 AC: 122083 AN: 151832 Hom.: 49707 Cov.: 32 AF XY: 0.807 AC XY: 59908 AN XY: 74218

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.821

Alfa AF: 0.771 Hom.: 1713

Bravo AF: 0.796

Asia WGS AF: 0.877 AC: 3052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs10839535; hg19: chr11-6292837;