11-34472254-C-T

Variant names:

• chr11-34472254-C-T
• rs475043
• NM_001752.4:c.*821C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001752.4(CAT):​c.*821C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,084 control chromosomes in the GnomAD database, including 40,526 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 0.71 (40526 hom., cov: 32)
• Consequence: CAT NM_001752.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.*821C>T		downstream_gene_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.*821C>T		downstream_gene_variant		1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108080 AN: 151966 Hom.: 40460 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.745

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.711 AC: 108203 AN: 152084 Hom.: 40526 Cov.: 32 AF XY: 0.706 AC XY: 52499 AN XY: 74318

African (AFR) AF: 0.918 AC: 38154 AN: 41542

American (AMR) AF: 0.770 AC: 11784 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3470

East Asian (EAS) AF: 0.970 AC: 5026 AN: 5182

South Asian (SAS) AF: 0.707 AC: 3404 AN: 4814

European-Finnish (FIN) AF: 0.441 AC: 4631 AN: 10498

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40434 AN: 67960

Other (OTH) AF: 0.748 AC: 1583 AN: 2116

Alfa AF: 0.650 Hom.: 41782

Bravo AF: 0.748

Asia WGS AF: 0.852 AC: 2964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		-0.040

Splicing

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

Other links and lift over

dbSNP: rs475043; hg19: chr11-34493801;