11-6270078-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

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>T		intron	N/A	NP_795344.1	P32239-1
	CCKBR	NM_001363552.2		c.404-10C>T		intron	N/A	NP_001350481.1	P32239-2
	CCKBR	NM_001318029.2		c.152-10C>T		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>T		intron	N/A	ENSP00000335544.2	P32239-1
	CCKBR	ENST00000525462.1	TSL:1	c.404-10C>T		intron	N/A	ENSP00000435534.1	P32239-2
	CCKBR	ENST00000912313.1		c.368-10C>T		intron	N/A	ENSP00000582372.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444840 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 715934

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33200

American (AMR) AF: 0.00 AC: 0 AN: 43986

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: 9.09e-7 AC: 1 AN: 1100618

Other (OTH) AF: 0.00 AC: 0 AN: 59568

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000360 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		0.11

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

Other links and lift over

dbSNP: rs78670873; hg19: chr11-6291308;