rs2179625

Positions:

• chr11-34445599-A-C
• chr11-34445599-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.67-3593A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,078 control chromosomes in the GnomAD database, including 3,759 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 0.21 (3759 hom., cov: 28)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

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=-0.9).
• 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	Protein	UniProt
CAT	NM_001752.4	c.67-3593A>C		intron_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.67-3593A>C		intron_variant		1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31569 AN: 150978 Hom.: 3760 Cov.: 28

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31567 AN: 151078 Hom.: 3759 Cov.: 28 AF XY: 0.206 AC XY: 15187 AN XY: 73770

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.246

Alfa AF: 0.250 Hom.: 4809

Bravo AF: 0.215

Asia WGS AF: 0.270 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.50

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: rs2179625; hg19: chr11-34467146;