rs2284367

Variant names:

• chr11-34462995-T-C
• rs2284367
• NM_001752.4:c.1196-1110T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-34462995-T-C
• chr11-34462995-T-G

Variant summary

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

The NM_001752.4(CAT):​c.1196-1110T>C 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 152,146 control chromosomes in the GnomAD database, including 4,296 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 0.23 (4296 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 14 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 = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1196-1110T>C		intron_variant	Intron 9 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1196-1110T>C		intron_variant	Intron 9 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000530343.1	n.658-1110T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34262 AN: 152026 Hom.: 4285 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.225 AC: 34298 AN: 152146 Hom.: 4296 Cov.: 32 AF XY: 0.227 AC XY: 16908 AN XY: 74376

African (AFR) AF: 0.162 AC: 6741 AN: 41504

American (AMR) AF: 0.305 AC: 4666 AN: 15286

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

East Asian (EAS) AF: 0.476 AC: 2469 AN: 5182

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4816

European-Finnish (FIN) AF: 0.197 AC: 2082 AN: 10592

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15449 AN: 67990

Other (OTH) AF: 0.270 AC: 568 AN: 2106

Alfa AF: 0.232 Hom.: 5420

Bravo AF: 0.235

Asia WGS AF: 0.339 AC: 1177 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	0.095
DANN	Benign	0.71
PhyloP100		-1.1
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: rs2284367; hg19: chr11-34484542;