11-34447777-A-G

Variant names:

• chr11-34447777-A-G
• rs533425
• NM_001752.4:c.67-1415A>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.67-1415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,200 control chromosomes in the GnomAD database, including 40,509 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 0.71 (40509 hom., cov: 33)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 8 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.67-1415A>G		intron_variant	Intron 1 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.67-1415A>G		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108080 AN: 152082 Hom.: 40438 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.711 AC: 108208 AN: 152200 Hom.: 40509 Cov.: 33 AF XY: 0.706 AC XY: 52517 AN XY: 74394

African (AFR) AF: 0.918 AC: 38141 AN: 41570

American (AMR) AF: 0.771 AC: 11799 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3470

East Asian (EAS) AF: 0.965 AC: 5007 AN: 5190

South Asian (SAS) AF: 0.709 AC: 3419 AN: 4824

European-Finnish (FIN) AF: 0.440 AC: 4643 AN: 10546

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40427 AN: 67982

Other (OTH) AF: 0.749 AC: 1585 AN: 2116

Alfa AF: 0.668 Hom.: 14615

Bravo AF: 0.748

Asia WGS AF: 0.852 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.37
PhyloP100		0.11
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: rs533425; hg19: chr11-34469324;