Variant chr2-201266864-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001372051.1(CASP8):c.305+73T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,141,694 control chromosomes in the GnomAD database, including 16,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4302 hom., cov: 31)

Exomes 𝑓: 0.12 ( 12042 hom. )

Consequence

CASP8
NM_001372051.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.299

Variant links:

Genes affected

CASP8 (HGNC:1509): (caspase 8) 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 composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. [provided by RefSeq, Jul 2008]

CASP8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 2-201266864-T-G is Benign according to our data. Variant chr2-201266864-T-G is described in ClinVar as [Benign]. Clinvar id is 1292384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP8	NM_001372051.1 linkuse as main transcript	c.305+73T>G		intron_variant		ENST00000673742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP8	ENST00000673742.1 linkuse as main transcript	c.305+73T>G		intron_variant			NM_001372051.1	P1	Q14790-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27958

AN:

151872

Hom.:

4275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.0871

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.0784

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.0751

Gnomad OTH

AF:

0.166

GnomAD4 exome

AF:

0.116

AC:

114603

AN:

989704

Hom.:

12042

AF XY:

0.125

AC XY:

62598

AN XY:

499018

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.0627

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.0847

Gnomad4 NFE exome

AF:

0.0759

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.185

AC:

28044

AN:

151990

Hom.:

4302

Cov.:

AF XY:

0.188

AC XY:

13964

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.0870

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.428

Gnomad4 FIN

AF:

0.0784

Gnomad4 NFE

AF:

0.0752

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.0973

Hom.:

2210

Bravo

AF:

0.189

Asia WGS

AF:

0.355

AC:

1236

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.1

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over