rs10488736

Positions:

• chr11-34467705-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001752.4(CAT):​c.1327-583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,786 control chromosomes in the GnomAD database, including 9,895 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 0.35 (9895 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAT	NM_001752.4	c.1327-583C>T		intron_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1327-583C>T		intron_variant		1	NM_001752.4	ENSP00000241052	P1
CAT	ENST00000525707.2	n.126-583C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52377 AN: 151668 Hom.: 9887 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.345 AC: 52424 AN: 151786 Hom.: 9895 Cov.: 32 AF XY: 0.337 AC XY: 24999 AN XY: 74206

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.364

Alfa AF: 0.322 Hom.: 10191

Bravo AF: 0.364

Asia WGS AF: 0.303 AC: 1056 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.61

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: rs10488736; hg19: chr11-34489252;