3-42261582-G-T

Variant names:

• chr3-42261582-G-T
• rs4377469
• NM_000729.6:c.214+1835C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000729.6(CCK):​c.214+1835C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 151,442 control chromosomes in the GnomAD database, including 47,940 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 0.78 (47940 hom., cov: 29)
• Consequence: CCK NM_000729.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722
• Publications: 17 publications found

Genes affected

CCK (HGNC:1569): (cholecystokinin) This gene encodes a member of the gastrin/cholecystokinin family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the peptide hormones cholecystokinin-8, -12, -33, and others. The encoded peptides have been shown to regulate gastric acid secretion and food intake. A sulfated form of cholecystokinin-8 may modulate neuronal activity in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000729.6. 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
	CCK	NM_000729.6	MANE Select	c.214+1835C>A		intron	N/A	NP_000720.1	Q6FG82
	CCK	NM_001174138.3		c.214+1835C>A		intron	N/A	NP_001167609.1	Q6FG82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCK	ENST00000396169.7	TSL:1 MANE Select	c.214+1835C>A		intron	N/A	ENSP00000379472.2	P06307
	CCK	ENST00000334681.9	TSL:1	c.214+1835C>A		intron	N/A	ENSP00000335657.5	P06307
	CCK	ENST00000434608.1	TSL:1	c.214+1835C>A		intron	N/A	ENSP00000409124.1	P06307

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118064 AN: 151332 Hom.: 47940 Cov.: 29

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.780 AC: 118100 AN: 151442 Hom.: 47940 Cov.: 29 AF XY: 0.783 AC XY: 57913 AN XY: 73938

African (AFR) AF: 0.539 AC: 22210 AN: 41184

American (AMR) AF: 0.796 AC: 12142 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3236 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3594 AN: 5128

South Asian (SAS) AF: 0.865 AC: 4157 AN: 4808

European-Finnish (FIN) AF: 0.923 AC: 9531 AN: 10324

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60408 AN: 67962

Other (OTH) AF: 0.814 AC: 1718 AN: 2110

Alfa AF: 0.843 Hom.: 135818

Bravo AF: 0.753

Asia WGS AF: 0.757 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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: rs4377469; hg19: chr3-42303074;