11-34438994-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001752.4(CAT):c.-20T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,575,640 control chromosomes in the GnomAD database, including 329,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.60 (28280 hom., cov: 34)
  • Exomes 𝑓: 0.65 (300865 hom.)
• Consequence: CAT NM_001752.4 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.144

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-34438994-T-C is Benign according to our data. Variant chr11-34438994-T-C is described in ClinVar as [Benign]. Clinvar id is 559060.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-34438994-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAT	NM_001752.4	c.-20T>C		5_prime_UTR_variant	1/13	ENST00000241052.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAT	ENST00000241052.5	c.-20T>C		5_prime_UTR_variant	1/13	1	NM_001752.4	P1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91687 AN: 152012 Hom.: 28263 Cov.: 34

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.583

GnomAD3 exomes AF: 0.589 AC: 113921 AN: 193292 Hom.: 34918 AF XY: 0.600 AC XY: 62625 AN XY: 104392

Gnomad AFR exome AF: 0.570

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.683

Gnomad EAS exome AF: 0.285

Gnomad SAS exome AF: 0.628

Gnomad FIN exome AF: 0.598

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.646 AC: 919429 AN: 1423512 Hom.: 300865 Cov.: 37 AF XY: 0.645 AC XY: 455170 AN XY: 705166

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.626

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.670

Gnomad4 OTH exome AF: 0.621

GnomAD4 genome AF: 0.603 AC: 91742 AN: 152128 Hom.: 28280 Cov.: 34 AF XY: 0.598 AC XY: 44509 AN XY: 74376

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.579

Alfa AF: 0.630 Hom.: 6329

Bravo AF: 0.589

Asia WGS AF: 0.451 AC: 1572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Oct 19, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.1
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1049982; hg19: chr11-34460541; COSMIC: COSV53810526;