rs2073058

Variant names:

• chr11-34456526-A-G
• rs2073058
• NM_001752.4:c.904-139A>G

Variant summary

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

The NM_001752.4(CAT):​c.904-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 848,472 control chromosomes in the GnomAD database, including 29,017 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 0.23 (4173 hom., cov: 33)
  • Exomes 𝑓: 0.26 (24844 hom.)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 10 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 = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.904-139A>G		intron_variant	Intron 7 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.904-139A>G		intron_variant	Intron 7 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000528104.2	n.274-139A>G		intron_variant	Intron 2 of 2	2
CAT	ENST00000650153.1	n.*724-139A>G		intron_variant	Intron 6 of 8			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34365 AN: 152140 Hom.: 4174 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.261 AC: 181644 AN: 696214 Hom.: 24844 AF XY: 0.264 AC XY: 98068 AN XY: 371158

African (AFR) AF: 0.174 AC: 3135 AN: 18052

American (AMR) AF: 0.273 AC: 10220 AN: 37450

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 6259 AN: 20828

East Asian (EAS) AF: 0.282 AC: 9515 AN: 33782

South Asian (SAS) AF: 0.328 AC: 21841 AN: 66558

European-Finnish (FIN) AF: 0.121 AC: 5421 AN: 44802

Middle Eastern (MID) AF: 0.336 AC: 1291 AN: 3846

European-Non Finnish (NFE) AF: 0.264 AC: 115114 AN: 435954

Other (OTH) AF: 0.253 AC: 8848 AN: 34942

GnomAD4 genome AF: 0.226 AC: 34365 AN: 152258 Hom.: 4173 Cov.: 33 AF XY: 0.221 AC XY: 16466 AN XY: 74446

African (AFR) AF: 0.175 AC: 7289 AN: 41556

American (AMR) AF: 0.253 AC: 3870 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1240 AN: 5186

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4816

European-Finnish (FIN) AF: 0.108 AC: 1146 AN: 10620

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17414 AN: 67994

Other (OTH) AF: 0.258 AC: 546 AN: 2114

Alfa AF: 0.251 Hom.: 6562

Bravo AF: 0.235

Asia WGS AF: 0.270 AC: 942 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	7.1
DANN	Benign	0.74
PhyloP100		-0.19
Mutation Taster		=100/0	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: rs2073058; hg19: chr11-34478073; COSMIC: COSV53812306; COSMIC: COSV53812306;