dbSNP rs12270780: CAT:c.66+85G>A (chr11-34439164-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_001752.4(CAT):c.66+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,297,586 control chromosomes in the GnomAD database, including 50,193 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 0.28 ( 6476 hom., cov: 33)

Exomes 𝑓: 0.27 ( 43717 hom. )

Consequence

CAT
NM_001752.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.210

Publications

14 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4 link	c.66+85G>A		intron_variant	Intron 1 of 12	ENST00000241052.5	NP_001743.1	P04040A0A384P5Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5 link	c.66+85G>A		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4		P04040

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43060

AN:

151970

Hom.:

6480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.271

AC:

310874

AN:

1145498

Hom.:

43717

AF XY:

0.273

AC XY:

156976

AN XY:

575598

show subpopulations

African (AFR)

AF:

0.347

AC:

9239

AN:

26660

American (AMR)

AF:

0.287

AC:

10136

AN:

35370

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

7119

AN:

23546

East Asian (EAS)

AF:

0.286

AC:

9887

AN:

34566

South Asian (SAS)

AF:

0.331

AC:

24528

AN:

74162

European-Finnish (FIN)

AF:

0.150

AC:

7143

AN:

47622

Middle Eastern (MID)

AF:

0.348

AC:

1596

AN:

4582

European-Non Finnish (NFE)

AF:

0.268

AC:

227539

AN:

849340

Other (OTH)

AF:

0.276

AC:

13687

AN:

49650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12284

24568

36851

49135

61419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7056

14112

21168

28224

35280

<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:

0.283

AC:

43065

AN:

152088

Hom.:

6476

Cov.:

AF XY:

0.278

AC XY:

20670

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.352

AC:

14600

AN:

41488

American (AMR)

AF:

0.276

AC:

4223

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1042

AN:

3464

East Asian (EAS)

AF:

0.241

AC:

1237

AN:

5138

South Asian (SAS)

AF:

0.341

AC:

1642

AN:

4818

European-Finnish (FIN)

AF:

0.138

AC:

1461

AN:

10616

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17991

AN:

67964

Other (OTH)

AF:

0.304

AC:

643

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1479

2958

4438

5917

7396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.275

Hom.:

19166

Bravo

AF:

0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.7

(source)

DANN

Benign

0.92

PhyloP100

0.21

PromoterAI

-0.15

Neutral

(source)

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

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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