rs2929183

Positions:

• chr11-6261578-G-A
• chr11-6261578-G-C
• chr11-6261578-G-T

Variant summary

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

The NM_176875.4(CCKBR):​c.151+1499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 150,864 control chromosomes in the GnomAD database, including 38,153 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 0.70 (38153 hom., cov: 27)
• Consequence: CCKBR NM_176875.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCKBR	NM_176875.4	c.151+1499G>A		intron_variant		ENST00000334619.7	NP_795344.1
CCKBR	NM_001363552.2	c.151+1499G>A		intron_variant			NP_001350481.1
CCKBR	NM_001318029.2	c.151+1499G>A		intron_variant			NP_001304958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCKBR	ENST00000334619.7	c.151+1499G>A		intron_variant		1	NM_176875.4	ENSP00000335544.2

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106133 AN: 150750 Hom.: 38133 Cov.: 27

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.724

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.704 AC: 106191 AN: 150864 Hom.: 38153 Cov.: 27 AF XY: 0.709 AC XY: 52217 AN XY: 73658

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.723

Alfa AF: 0.744 Hom.: 29402

Bravo AF: 0.701

Asia WGS AF: 0.821 AC: 2852 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.55

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: rs2929183; hg19: chr11-6282808;