11-6269701-G-T

Variant names:

• chr11-6269701-G-T
• rs141038981
• NM_176875.4:c.184G>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.184G>T​(p.Ala62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A62T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCKBR NM_176875.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• 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 (MetaRNN=0.058548898).

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.184G>T	p.Ala62Ser	missense	Exon 2 of 5	NP_795344.1	P32239-1
	CCKBR	NM_001363552.2		c.184G>T	p.Ala62Ser	missense	Exon 2 of 4	NP_001350481.1	P32239-2
	CCKBR	NM_001318029.2		c.152-387G>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.184G>T	p.Ala62Ser	missense	Exon 2 of 5	ENSP00000335544.2	P32239-1
	CCKBR	ENST00000525462.1	TSL:1	c.184G>T	p.Ala62Ser	missense	Exon 2 of 4	ENSP00000435534.1	P32239-2
	CCKBR	ENST00000912313.1		c.152-4G>T		splice_region intron	N/A	ENSP00000582372.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251310 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461680 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727166

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111934

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.45
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.27
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.012
Sift	Benign	0.84	T
Sift4G	Benign	0.83	T
Polyphen		0.0030	B
Vest4		0.11
MutPred		0.44		Gain of sheet (P = 0.1208)
MVP		0.47
MPC		0.31
ClinPred		0.13	T
GERP RS		2.7
Varity_R		0.027
gMVP		0.19
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs141038981; hg19: chr11-6290931;