chr11-6270078-C-G

Variant names:

• chr11-6270078-C-G
• rs78670873
• NM_176875.4:c.404-10C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_176875.4(CCKBR):​c.404-10C>G variant causes a 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 intron
• Scores: Splicing: ADA: 0.0008538
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.110
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176875.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCKBR	NM_176875.4	MANE Select	c.404-10C>G		intron	N/A	NP_795344.1	P32239-1
	CCKBR	NM_001363552.2		c.404-10C>G		intron	N/A	NP_001350481.1	P32239-2
	CCKBR	NM_001318029.2		c.152-10C>G		intron	N/A	NP_001304958.1	E9PIC8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCKBR	ENST00000334619.7	TSL:1 MANE Select	c.404-10C>G		intron	N/A	ENSP00000335544.2	P32239-1
	CCKBR	ENST00000525462.1	TSL:1	c.404-10C>G		intron	N/A	ENSP00000435534.1	P32239-2
	CCKBR	ENST00000912313.1		c.368-10C>G		intron	N/A	ENSP00000582372.1

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 334 AN: 152226 Hom.: 3 Cov.: 32

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

GnomAD2 exomes AF: 0.00805 AC: 1935 AN: 240498 AF XY: 0.00579

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 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.: 69 Cov.: 33 AF XY: 0.00127 AC XY: 907 AN XY: 715930

African (AFR) AF: 0.000452 AC: 15 AN: 33200

American (AMR) AF: 0.0498 AC: 2192 AN: 43980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39388

South Asian (SAS) AF: 0.00 AC: 0 AN: 84470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.0000227 AC: 25 AN: 1100618

Other (OTH) AF: 0.00101 AC: 60 AN: 59568

GnomAD4 genome AF: 0.00217 AC: 331 AN: 152344 Hom.: 3 Cov.: 32 AF XY: 0.00244 AC XY: 182 AN XY: 74504

African (AFR) AF: 0.000794 AC: 33 AN: 41580

American (AMR) AF: 0.0189 AC: 290 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000288 Hom.: 0

Bravo AF: 0.00483

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.58
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78670873; hg19: chr11-6291308;