Genetic Variant CASP7:c.-282G>T (chr10-113679771-G-T) – 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 ENST00000345633.8(CASP7):c.-282G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000866 in 1,154,560 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.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

CASP7
ENST00000345633.8 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.21

Publications

15 publications found

Variant links:

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CASP7 links:

Genome browser will be placed here

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=0.13997638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000345633.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CASP7	NM_001267057.1	c.17G>T	p.Arg6Leu	missense	Exon 1 of 7	NP_001253986.1	P55210
CASP7	NM_001320911.2	c.-8+422G>T		intron	N/A	NP_001307840.1
CASP7	NM_001267056.2	c.-1+422G>T		intron	N/A	NP_001253985.1	P55210-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CASP7	ENST00000345633.8	TSL:1	c.-282G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000298701.7	P55210-1
CASP7	ENST00000345633.8	TSL:1	c.-282G>T	5_prime_UTR	Exon 1 of 8	ENSP00000298701.7	P55210-1
CASP7	ENST00000621345.4	TSL:1	c.-1+422G>T	intron	N/A	ENSP00000480584.1	P55210-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.66e-7

AC:

AN:

1154560

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

554522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23890

American (AMR)

AF:

0.00

AC:

AN:

13708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15944

East Asian (EAS)

AF:

0.00

AC:

AN:

27780

South Asian (SAS)

AF:

0.00

AC:

AN:

42806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3154

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

954512

Other (OTH)

AF:

0.00

AC:

AN:

46780

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.30

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.00041

LIST_S2

Benign

0.35

MetaRNN

Benign

0.14

PhyloP100

-2.2

PrimateAI

Uncertain

0.57

Vest4

0.17

MVP

0.76

GERP RS

-4.4

PromoterAI

-0.025

Neutral

(source)

gMVP

0.072

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over