rs12270780

Positions:

• chr11-34439164-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001752.4(CAT):​c.66+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,297,586 control chromosomes in the GnomAD database, including 50,193 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 0.28 (6476 hom., cov: 33)
  • Exomes 𝑓: 0.27 (43717 hom.)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAT	NM_001752.4	c.66+85G>A		intron_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.66+85G>A		intron_variant		1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43060 AN: 151970 Hom.: 6480 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.271 AC: 310874 AN: 1145498 Hom.: 43717 AF XY: 0.273 AC XY: 156976 AN XY: 575598

Gnomad4 AFR exome AF: 0.347

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.283 AC: 43065 AN: 152088 Hom.: 6476 Cov.: 33 AF XY: 0.278 AC XY: 20670 AN XY: 74364

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.304

Alfa AF: 0.278 Hom.: 7261

Bravo AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.92

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: rs12270780; hg19: chr11-34460711; COSMIC: COSV53814249;