Genetic Variant CAT:c.-89A>T (chr11-34438925-A-T) – 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.-89A>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,178,738 control chromosomes in the GnomAD database, including 236,522 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 0.57 ( 25476 hom., cov: 33)

Exomes 𝑓: 0.64 ( 211046 hom. )

Consequence

CAT
NM_001752.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.932

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 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4 link	c.-89A>T		upstream_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.-89A>T		upstream_gene_variant		1	NM_001752.4	ENSP00000241052.4		P04040

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

86025

AN:

151930

Hom.:

25462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.634

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.560

GnomAD4 exome

AF:

0.636

AC:

652535

AN:

1026688

Hom.:

211046

Cov.:

AF XY:

0.636

AC XY:

331698

AN XY:

521190

show subpopulations

African (AFR)

AF:

0.439

AC:

10698

AN:

24384

American (AMR)

AF:

0.453

AC:

15980

AN:

35272

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

15573

AN:

22834

East Asian (EAS)

AF:

0.317

AC:

10810

AN:

34072

South Asian (SAS)

AF:

0.627

AC:

45084

AN:

71876

European-Finnish (FIN)

AF:

0.596

AC:

28671

AN:

48096

Middle Eastern (MID)

AF:

0.620

AC:

3108

AN:

5012

European-Non Finnish (NFE)

AF:

0.669

AC:

494800

AN:

739466

Other (OTH)

AF:

0.609

AC:

27811

AN:

45676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

12722

25443

38165

50886

63608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.566

AC:

86072

AN:

152050

Hom.:

25476

Cov.:

AF XY:

0.563

AC XY:

41819

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.441

AC:

18279

AN:

41456

American (AMR)

AF:

0.496

AC:

7586

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2346

AN:

3472

East Asian (EAS)

AF:

0.282

AC:

1451

AN:

5150

South Asian (SAS)

AF:

0.634

AC:

3055

AN:

4822

European-Finnish (FIN)

AF:

0.606

AC:

6417

AN:

10584

Middle Eastern (MID)

AF:

0.606

AC:

177

AN:

292

European-Non Finnish (NFE)

AF:

0.664

AC:

45095

AN:

67962

Other (OTH)

AF:

0.555

AC:

1172

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1874

3748

5622

7496

9370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.607

Hom.:

3562

Bravo

AF:

0.547

Asia WGS

AF:

0.441

AC:

1535

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.5

(source)

DANN

Benign

0.36

PhyloP100

-0.93

PromoterAI

-0.19

Neutral

(source)

Mutation Taster

=300/0

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

LitVar

Below is the list of publications found by LitVar for variant 11:34438925 A>T . It may be empty.

chr11-34438925-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over