11-34438994-T-C

Variant names:

• chr11-34438994-T-C
• rs1049982
• NM_001752.4:c.-20T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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 (★).

• 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 criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.144
• Publications: 53 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 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 criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.-20T>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.-20T>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_001752.4	ENSP00000241052.4

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

GnomAD2 exomes AF: 0.589 AC: 113921 AN: 193292 AF XY: 0.600

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 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

African (AFR) AF: 0.571 AC: 18576 AN: 32504

American (AMR) AF: 0.456 AC: 18193 AN: 39894

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17474 AN: 25546

East Asian (EAS) AF: 0.330 AC: 12332 AN: 37372

South Asian (SAS) AF: 0.626 AC: 51282 AN: 81856

European-Finnish (FIN) AF: 0.596 AC: 29755 AN: 49886

Middle Eastern (MID) AF: 0.622 AC: 3563 AN: 5728

European-Non Finnish (NFE) AF: 0.670 AC: 731673 AN: 1091854

Other (OTH) AF: 0.621 AC: 36581 AN: 58872

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

African (AFR) AF: 0.571 AC: 23712 AN: 41496

American (AMR) AF: 0.504 AC: 7708 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2347 AN: 3472

East Asian (EAS) AF: 0.287 AC: 1476 AN: 5146

South Asian (SAS) AF: 0.633 AC: 3055 AN: 4828

European-Finnish (FIN) AF: 0.606 AC: 6418 AN: 10590

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45132 AN: 67986

Other (OTH) AF: 0.579 AC: 1220 AN: 2108

Alfa AF: 0.629 Hom.: 6462

Bravo AF: 0.589

Asia WGS AF: 0.451 AC: 1572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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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
PhyloP100		0.14
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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