Genetic Variant CAAP1:p.Ala209Val (chr9-26884849-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024828.4(CAAP1):c.626C>T(p.Ala209Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CAAP1
NM_024828.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Publications

0 publications found

Variant links:

Genes affected

CAAP1 (HGNC:25834): (caspase activity and apoptosis inhibitor 1) Involved in negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

CAAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23766771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAAP1	NM_024828.4 link	c.626C>T	p.Ala209Val	missense_variant	Exon 4 of 6	ENST00000333916.8	NP_079104.3	Q9H8G2-1
CAAP1	NM_001167575.2 link	c.191C>T	p.Ala64Val	missense_variant	Exon 4 of 6		NP_001161047.1	Q9H8G2-2
CAAP1	XM_047423896.1 link	c.626C>T	p.Ala209Val	missense_variant	Exon 4 of 6		XP_047279852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8 link	c.626C>T	p.Ala209Val	missense_variant	Exon 4 of 6	1	NM_024828.4	ENSP00000369431.3		Q9H8G2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457282

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.00

AC:

AN:

86146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111146

Other (OTH)

AF:

0.0000332

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 31, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.626C>T (p.A209V) alteration is located in exon 4 (coding exon 4) of the CAAP1 gene. This alteration results from a C to T substitution at nucleotide position 626, causing the alanine (A) at amino acid position 209 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.83

PhyloP100

4.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.22

Sift

Uncertain

0.025

D;.

Sift4G

Benign

0.11

T;T

Polyphen

0.99

D;.

Vest4

0.26

MutPred

0.099

Loss of helix (P = 0.1299);.;

MVP

0.33

MPC

0.60

ClinPred

0.86

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.12

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over