11-34459548-G-T

Variant names:

• chr11-34459548-G-T
• rs10836244
• NM_001752.4:c.1057-1703G>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.1057-1703G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,136 control chromosomes in the GnomAD database, including 4,308 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 (4308 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001752.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	NM_001752.4	MANE Select	c.1057-1703G>T		intron	N/A	NP_001743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	ENST00000241052.5	TSL:1 MANE Select	c.1057-1703G>T		intron	N/A	ENSP00000241052.4
	CAT	ENST00000650153.1		n.*948+1701G>T		intron	N/A	ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34343 AN: 152018 Hom.: 4298 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.226 AC: 34379 AN: 152136 Hom.: 4308 Cov.: 32 AF XY: 0.228 AC XY: 16951 AN XY: 74364

African (AFR) AF: 0.165 AC: 6831 AN: 41514

American (AMR) AF: 0.306 AC: 4670 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2459 AN: 5158

South Asian (SAS) AF: 0.220 AC: 1062 AN: 4820

European-Finnish (FIN) AF: 0.197 AC: 2085 AN: 10596

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

European-Non Finnish (NFE) AF: 0.227 AC: 15435 AN: 67980

Other (OTH) AF: 0.272 AC: 573 AN: 2110

Alfa AF: 0.235 Hom.: 5780

Bravo AF: 0.235

Asia WGS AF: 0.339 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.79
PhyloP100		0.088
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: rs10836244; hg19: chr11-34481095;