Genetic Variant NM_024828.4:c.249G>T (chr9-26892467-C-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.249G>T(p.Glu83Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,567,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CAAP1
NM_024828.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

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:

ENSG00000295750 (HGNC:):

ENSG00000295750 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=0.11881086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAAP1	NM_024828.4 link	c.249G>T	p.Glu83Asp	missense_variant	Exon 1 of 6	ENST00000333916.8	NP_079104.3	Q9H8G2-1
CAAP1	XM_047423896.1 link	c.249G>T	p.Glu83Asp	missense_variant	Exon 1 of 6		XP_047279852.1
CAAP1	NM_001167575.2 link	c.-341G>T		5_prime_UTR_variant	Exon 1 of 6		NP_001161047.1	Q9H8G2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8 link	c.249G>T	p.Glu83Asp	missense_variant	Exon 1 of 6	1	NM_024828.4	ENSP00000369431.3		Q9H8G2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000619

AC:

AN:

161674

AF XY:

0.0000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000828

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1415038

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32242

American (AMR)

AF:

0.00

AC:

AN:

38382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25326

East Asian (EAS)

AF:

0.0000272

AC:

AN:

36792

South Asian (SAS)

AF:

0.00

AC:

AN:

81570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089318

Other (OTH)

AF:

0.00

AC:

AN:

58638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000861

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

PhyloP100

1.8

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.0

N;D

REVEL

Benign

0.038

Sift

Benign

0.033

D;D

Sift4G

Benign

0.60

T;T

Polyphen

0.37

B;.

Vest4

0.40

MutPred

0.11

Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.15

MPC

0.12

ClinPred

0.20

GERP RS

1.1

PromoterAI

0.15

Neutral

(source)

Varity_R

0.17

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(source)

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

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NM_024828.4:c.249G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over