rs480575

Variant names:

• chr11-34446099-A-G
• rs480575
• NM_001752.4:c.67-3093A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-34446099-A-G
• chr11-34446099-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001752.4(CAT):​c.67-3093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,954 control chromosomes in the GnomAD database, including 8,326 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 0.31 (8326 hom., cov: 31)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 27 publications found

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]

CAT Gene-Disease associations (from GenCC):

• acatalasia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.67-3093A>G		intron_variant	Intron 1 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.67-3093A>G		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47693 AN: 151836 Hom.: 8307 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.314 AC: 47753 AN: 151954 Hom.: 8326 Cov.: 31 AF XY: 0.319 AC XY: 23698 AN XY: 74254

African (AFR) AF: 0.251 AC: 10404 AN: 41448

American (AMR) AF: 0.439 AC: 6701 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1087 AN: 3466

East Asian (EAS) AF: 0.712 AC: 3667 AN: 5152

South Asian (SAS) AF: 0.344 AC: 1655 AN: 4808

European-Finnish (FIN) AF: 0.310 AC: 3261 AN: 10536

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19774 AN: 67960

Other (OTH) AF: 0.354 AC: 746 AN: 2108

Alfa AF: 0.299 Hom.: 13188

Bravo AF: 0.325

Asia WGS AF: 0.528 AC: 1832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.69
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs480575; hg19: chr11-34467646;