rs2073058

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.253

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

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.258

Alfa AF: 0.253 Hom.: 5110

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

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: rs2073058; hg19: chr11-34478073; COSMIC: COSV53812306; COSMIC: COSV53812306;