11-34438684-C-T

Variant names:

• chr11-34438684-C-T
• rs1001179
• NM_001752.4:c.-330C>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.-330C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,256 control chromosomes in the GnomAD database, including 2,534 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 0.16 (2534 hom., cov: 33)
• Consequence: CAT NM_001752.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 362 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.-330C>T		upstream_gene_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.-330C>T		upstream_gene_variant		1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24722 AN: 152138 Hom.: 2534 Cov.: 33

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.162 AC: 24717 AN: 152256 Hom.: 2534 Cov.: 33 AF XY: 0.167 AC XY: 12426 AN XY: 74444

African (AFR) AF: 0.0464 AC: 1930 AN: 41584

American (AMR) AF: 0.132 AC: 2023 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3470

East Asian (EAS) AF: 0.0338 AC: 175 AN: 5174

South Asian (SAS) AF: 0.225 AC: 1087 AN: 4824

European-Finnish (FIN) AF: 0.272 AC: 2882 AN: 10590

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15203 AN: 67994

Other (OTH) AF: 0.155 AC: 328 AN: 2110

Alfa AF: 0.202 Hom.: 9346

Bravo AF: 0.145

Asia WGS AF: 0.115 AC: 401 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	5.5
DANN	Benign	0.59
PhyloP100		-0.35
PromoterAI		0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1001179; hg19: chr11-34460231; COSMIC: COSV53812973;