rs7104301

Positions:

• chr11-34472091-A-G

Variant summary

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

The 11-34472091-A-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,942 control chromosomes in the GnomAD database, including 4,134 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 0.22 (4115 hom., cov: 33)
  • Exomes 𝑓: 0.23 (19 hom.)
• Consequence: CAT NM_001752.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951

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=-0.91).
• 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/exons	MANE	UniProt
CAT	NM_001752.4			downstream_gene_variant		ENST00000241052.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAT	ENST00000241052.5			downstream_gene_variant		1	NM_001752.4	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34093 AN: 152032 Hom.: 4115 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.234 AC: 185 AN: 792 Hom.: 19 Cov.: 0 AF XY: 0.235 AC XY: 102 AN XY: 434

Gnomad4 AMR exome AF: 0.227

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.224 AC: 34104 AN: 152150 Hom.: 4115 Cov.: 33 AF XY: 0.220 AC XY: 16338 AN XY: 74374

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.259

Alfa AF: 0.261 Hom.: 5269

Bravo AF: 0.233

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.092
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7104301; hg19: chr11-34493638;