rs12269988

chr11-34451227-A-G

Variant summary

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

The NM_001752.4(CAT):c.349+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0454 in 727,814 control chromosomes in the GnomAD database, including 998 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 0.060 (337 hom., cov: 32)
  • Exomes 𝑓: 0.042 (661 hom.)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAT	NM_001752.4	c.349+129A>G		intron_variant		ENST00000241052.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAT	ENST00000241052.5	c.349+129A>G		intron_variant		1	NM_001752.4	P1
CAT	ENST00000650153.1	c.*169+129A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9055 AN: 152198 Hom.: 337 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0416 AC: 23929 AN: 575498 Hom.: 661 AF XY: 0.0412 AC XY: 12848 AN XY: 312076

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0253

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.0000303

Gnomad4 SAS exome AF: 0.0275

Gnomad4 FIN exome AF: 0.0242

Gnomad4 NFE exome AF: 0.0445

Gnomad4 OTH exome AF: 0.0499

GnomAD4 genome AF: 0.0596 AC: 9080 AN: 152316 Hom.: 337 Cov.: 32 AF XY: 0.0571 AC XY: 4254 AN XY: 74490

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0455

Gnomad4 OTH AF: 0.0600

Alfa AF: 0.0478 Hom.: 212

Bravo AF: 0.0625

Asia WGS AF: 0.0190 AC: 67 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	6.8
Dann	Benign	0.78

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: rs12269988; hg19: chr11-34472774;