chr11-34463426-T-C

Position:

• chr11-34463426-T-C

Variant summary

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

The NM_001752.4(CAT):​c.1196-679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,052 control chromosomes in the GnomAD database, including 5,892 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 0.27 (5892 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAT	NM_001752.4	c.1196-679T>C		intron_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1196-679T>C		intron_variant		1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000530343.1	n.658-679T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40890 AN: 151934 Hom.: 5878 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.269 AC: 40945 AN: 152052 Hom.: 5892 Cov.: 32 AF XY: 0.270 AC XY: 20079 AN XY: 74332

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.298

Alfa AF: 0.243 Hom.: 7922

Bravo AF: 0.285

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.14
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2284365; hg19: chr11-34484973;