Variant chr11-105031189-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001257118.3(CASP1):c.429G>A(p.Arg143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,611,706 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 32 hom. )

Consequence

CASP1
NM_001257118.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.990

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-105031189-C-T is Benign according to our data. Variant chr11-105031189-C-T is described in ClinVar as [Benign]. Clinvar id is 709976.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.99 with no splicing effect.

BS2

High AC in GnomAd4 at 720 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP1	NM_001257118.3 linkuse as main transcript	c.429G>A	p.Arg143=	synonymous_variant	4/9	ENST00000533400.6
LOC124902742	XR_007062869.1 linkuse as main transcript	n.41-158C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP1	ENST00000533400.6 linkuse as main transcript	c.429G>A	p.Arg143=	synonymous_variant	4/9	1	NM_001257118.3	P2	P29466-1

Frequencies

GnomAD3 genomes

AF:

0.00473

AC:

720

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0171

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00675

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00478

AC:

1199

AN:

250870

Hom.:

AF XY:

0.00464

AC XY:

629

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000842

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.00703

Gnomad OTH exome

AF:

0.00410

GnomAD4 exome

AF:

0.00436

AC:

6358

AN:

1459442

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

3192

AN XY:

726166

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.000614

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0153

Gnomad4 NFE exome

AF:

0.00471

Gnomad4 OTH exome

AF:

0.00360

GnomAD4 genome

AF:

0.00473

AC:

720

AN:

152264

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

364

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0171

Gnomad4 NFE

AF:

0.00675

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.00279

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00368

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

DANN

Benign

0.43

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

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