dbSNP rs1434803452: CCK:p.Arg70Trp (chr3-42263423-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000729.6(CCK):c.208C>T(p.Arg70Trp) 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 1,461,872 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCK
NM_000729.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.446

Variant links:

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]

CCK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4226743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCK	NM_000729.6 link	c.208C>T	p.Arg70Trp	missense_variant	Exon 4 of 5	ENST00000396169.7	NP_000720.1	P06307Q6FG82
CCK	NM_001174138.3 link	c.208C>T	p.Arg70Trp	missense_variant	Exon 2 of 3		NP_001167609.1	P06307Q6FG82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCK	ENST00000396169.7 link	c.208C>T	p.Arg70Trp	missense_variant	Exon 4 of 5	1	NM_000729.6	ENSP00000379472.2	P06307
CCK	ENST00000334681.9 link	c.208C>T	p.Arg70Trp	missense_variant	Exon 2 of 3	1		ENSP00000335657.5	P06307
CCK	ENST00000434608.1 link	c.208C>T	p.Arg70Trp	missense_variant	Exon 2 of 3	1		ENSP00000409124.1	P06307
CCK	ENST00000484359.1 link	n.279C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.90

.;.;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.89

P;P;P

Vest4

0.43

MutPred

0.58

Loss of disorder (P = 0.0022);Loss of disorder (P = 0.0022);Loss of disorder (P = 0.0022);

MVP

0.59

MPC

1.9

ClinPred

1.0

GERP RS

-2.6

Varity_R

0.66

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over