rs566979

chr11-34469100-A-Cchr11-34469100-A-T

Variant summary

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

The NM_001752.4(CAT):c.1434+705A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,034 control chromosomes in the GnomAD database, including 14,973 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 0.43 (14973 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAT	NM_001752.4	c.1434+705A>C		intron_variant		ENST00000241052.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAT	ENST00000241052.5	c.1434+705A>C		intron_variant		1	NM_001752.4	P1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65351 AN: 151916 Hom.: 14952 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.430 AC: 65416 AN: 152034 Hom.: 14973 Cov.: 32 AF XY: 0.424 AC XY: 31519 AN XY: 74296

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.440

Alfa AF: 0.374 Hom.: 10048

Bravo AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.27
Dann	Benign	0.49

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: rs566979; hg19: chr11-34490647;