rs2284369

Variant names:

• chr11-34447389-A-G
• rs2284369
• NM_001752.4:c.67-1803A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-34447389-A-G
• chr11-34447389-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.67-1803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,992 control chromosomes in the GnomAD database, including 4,271 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 (4271 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 22 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.67-1803A>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.67-1803A>G		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34088 AN: 151874 Hom.: 4258 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.225 AC: 34135 AN: 151992 Hom.: 4271 Cov.: 32 AF XY: 0.227 AC XY: 16848 AN XY: 74298

African (AFR) AF: 0.158 AC: 6567 AN: 41440

American (AMR) AF: 0.306 AC: 4678 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3468

East Asian (EAS) AF: 0.479 AC: 2463 AN: 5146

South Asian (SAS) AF: 0.221 AC: 1067 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2084 AN: 10566

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15436 AN: 67958

Other (OTH) AF: 0.274 AC: 576 AN: 2102

Alfa AF: 0.226 Hom.: 6902

Bravo AF: 0.233

Asia WGS AF: 0.345 AC: 1199 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	2.7
DANN	Benign	0.69
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2284369; hg19: chr11-34468936;