dbSNP rs7104301: CAT:c.*658A>G (chr11-34472091-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001752.4(CAT):c.*658A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,942 control chromosomes in the GnomAD database, including 4,134 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 0.22 ( 4115 hom., cov: 33)

Exomes 𝑓: 0.23 ( 19 hom. )

Consequence

CAT
NM_001752.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.951

Publications

12 publications found

Variant links:

Genes affected

CAT (HGNC:1516): (catalase) This gene encodes catalase, a key antioxidant enzyme in the bodies defense against oxidative stress. Catalase is a heme enzyme that is present in the peroxisome of nearly all aerobic cells. Catalase converts the reactive oxygen species hydrogen peroxide to water and oxygen and thereby mitigates the toxic effects of hydrogen peroxide. Oxidative stress is hypothesized to play a role in the development of many chronic or late-onset diseases such as diabetes, asthma, Alzheimer's disease, systemic lupus erythematosus, rheumatoid arthritis, and cancers. Polymorphisms in this gene have been associated with decreases in catalase activity but, to date, acatalasemia is the only disease known to be caused by this gene. [provided by RefSeq, Oct 2009]

CAT Gene-Disease associations (from GenCC):

acatalasia
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

CAT 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4 link	c.*658A>G		downstream_gene_variant		ENST00000241052.5	NP_001743.1	P04040A0A384P5Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5 link	c.*658A>G		downstream_gene_variant		1	NM_001752.4	ENSP00000241052.4		P04040

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34093

AN:

152032

Hom.:

4115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.234

AC:

185

AN:

792

Hom.:

Cov.:

AF XY:

0.235

AC XY:

102

AN XY:

434

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.227

AC:

AN:

128

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.211

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.236

AC:

130

AN:

552

Other (OTH)

AF:

0.364

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.224

AC:

34104

AN:

152150

Hom.:

4115

Cov.:

AF XY:

0.220

AC XY:

16338

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.169

AC:

7011

AN:

41524

American (AMR)

AF:

0.253

AC:

3867

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1042

AN:

3470

East Asian (EAS)

AF:

0.239

AC:

1236

AN:

5178

South Asian (SAS)

AF:

0.337

AC:

1625

AN:

4820

European-Finnish (FIN)

AF:

0.109

AC:

1157

AN:

10600

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17419

AN:

67970

Other (OTH)

AF:

0.259

AC:

547

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1318

2636

3954

5272

6590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.257

Hom.:

6719

Bravo

AF:

0.233

Asia WGS

AF:

0.275

AC:

959

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.092

(source)

DANN

Benign

0.47

PhyloP100

-0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over