Variant 11-105029658-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001257118.3(CASP1):c.862+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,596,892 control chromosomes in the GnomAD database, including 23,320 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2034 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21286 hom. )

Consequence

CASP1
NM_001257118.3 splice_region, intron

Scores

Splicing: ADA: 0.00008079

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.267

Variant links:

Genes affected

CASP1 (HGNC:1499): (caspase 1) This gene encodes a protein which is 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 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

CASP1 links:

LOC124902742 (HGNC:):

LOC124902742 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP1	NM_001257118.3 linkuse as main transcript	c.862+7G>A		splice_region_variant, intron_variant		ENST00000533400.6	NP_001244047.1
LOC124902742	XR_007062869.1 linkuse as main transcript	n.41-1689C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6 linkuse as main transcript	c.862+7G>A		splice_region_variant, intron_variant		1	NM_001257118.3	ENSP00000433138	P2	P29466-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23174

AN:

152008

Hom.:

2030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0977

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.172

AC:

42936

AN:

250150

Hom.:

4625

AF XY:

0.165

AC XY:

22281

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.00463

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.164

AC:

236974

AN:

1444766

Hom.:

21286

Cov.:

AF XY:

0.161

AC XY:

116093

AN XY:

719930

show subpopulations

Gnomad4 AFR exome

AF:

0.0949

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.00230

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.153

AC:

23200

AN:

152126

Hom.:

2034

Cov.:

AF XY:

0.155

AC XY:

11540

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0980

Gnomad4 AMR

AF:

0.246

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.159

Hom.:

1425

Bravo

AF:

0.155

Asia WGS

AF:

0.0760

AC:

262

AN:

3478

EpiCase

AF:

0.154

EpiControl

AF:

0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.2

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000081

dbscSNV1_RF

Benign

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over