Variant rs61751523 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.956A>G(p.Lys319Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,613,270 control chromosomes in the GnomAD database, including 515 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.036 ( 174 hom., cov: 32)

Exomes 𝑓: 0.014 ( 341 hom. )

Consequence

CASP1
NM_001257118.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.651

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 (MetaRNN=0.002117306).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP1	NM_001257118.3 linkuse as main transcript	c.956A>G	p.Lys319Arg	missense_variant	7/9	ENST00000533400.6
LOC124902742	XR_007062869.1 linkuse as main transcript	n.41-2173T>C		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.956A>G	p.Lys319Arg	missense_variant	7/9	1	NM_001257118.3	P2	P29466-1

Frequencies

GnomAD3 genomes

AF:

0.0360

AC:

5475

AN:

152128

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0891

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.0438

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0420

GnomAD3 exomes

AF:

0.0222

AC:

5576

AN:

250894

Hom.:

130

AF XY:

0.0213

AC XY:

2891

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.0942

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.0463

Gnomad SAS exome

AF:

0.0217

Gnomad FIN exome

AF:

0.00967

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0141

AC:

20612

AN:

1461024

Hom.:

341

Cov.:

AF XY:

0.0141

AC XY:

10235

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.0966

Gnomad4 AMR exome

AF:

0.0196

Gnomad4 ASJ exome

AF:

0.0288

Gnomad4 EAS exome

AF:

0.0290

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.00895

Gnomad4 NFE exome

AF:

0.00966

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0360

AC:

5477

AN:

152246

Hom.:

174

Cov.:

AF XY:

0.0353

AC XY:

2628

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0889

Gnomad4 AMR

AF:

0.0253

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.0437

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0402

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.0815

AC:

359

ESP6500EA

AF:

0.0120

AC:

103

ExAC

AF:

0.0226

AC:

2743

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0155

EpiControl

AF:

0.0150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.75

Cadd

Benign

3.0

Dann

Benign

0.61

DEOGEN2

Benign

0.010

T;.;.;T;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.043

T;T;T;.;T;T;T

MetaRNN

Benign

0.0021

T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.65

N;N;N;N;N;N;N

REVEL

Benign

0.018

Sift

Benign

0.95

T;T;T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T;T;T

Polyphen

0.0

.;B;B;B;B;B;B

Vest4

0.031, 0.028, 0.033, 0.034

MPC

0.13

ClinPred

0.0012

GERP RS

-0.82

Varity_R

0.23

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over