dbSNP rs5030551: CASP6:c.84-126C>T (chr4-109697894-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001226.4(CASP6):c.84-126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00587 in 1,047,886 control chromosomes in the GnomAD database, including 249 homozygotes. 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: 𝑓 0.025 ( 172 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 77 hom. )

Consequence

CASP6
NM_001226.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.850

Publications

3 publications found

Variant links:

Genes affected

CASP6 (HGNC:1507): (caspase 6) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. 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 acid residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Alternative splicing of this gene results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Oct 2015]

CASP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CASP6	NM_001226.4	MANE Select	c.84-126C>T	intron	N/A	NP_001217.2
CASP6	NM_032992.3		c.41-3194C>T	intron	N/A	NP_116787.1
CASP6	NR_133012.2		n.134-126C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CASP6	ENST00000265164.7	TSL:1 MANE Select	c.84-126C>T	intron	N/A	ENSP00000265164.2
CASP6	ENST00000352981.7	TSL:1	c.41-3194C>T	intron	N/A	ENSP00000285333.3
CASP6	ENST00000503684.5	TSL:3	c.30-126C>T	intron	N/A	ENSP00000427669.1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3807

AN:

152146

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0880

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0158

GnomAD4 exome

AF:

0.00261

AC:

2338

AN:

895622

Hom.:

AF XY:

0.00235

AC XY:

1064

AN XY:

452902

show subpopulations

African (AFR)

AF:

0.0873

AC:

1783

AN:

20418

American (AMR)

AF:

0.00415

AC:

AN:

23160

Ashkenazi Jewish (ASJ)

AF:

0.000176

AC:

AN:

17046

East Asian (EAS)

AF:

0.0000292

AC:

AN:

34298

South Asian (SAS)

AF:

0.000254

AC:

AN:

55022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36106

Middle Eastern (MID)

AF:

0.00444

AC:

AN:

3828

European-Non Finnish (NFE)

AF:

0.000299

AC:

199

AN:

664958

Other (OTH)

AF:

0.00552

AC:

225

AN:

40786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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

AF:

0.0251

AC:

3817

AN:

152264

Hom.:

172

Cov.:

AF XY:

0.0233

AC XY:

1736

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0880

AC:

3655

AN:

41532

American (AMR)

AF:

0.00693

AC:

106

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68022

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

179

359

538

718

897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0285

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.98

(source)

DANN

Benign

0.79

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over