rs480496

Variant names:

• chr11-34467282-A-G
• rs480496
• NM_001752.4:c.1327-1006A>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.1327-1006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,124 control chromosomes in the GnomAD database, including 28,556 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 0.58 (28556 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1327-1006A>G		intron_variant	Intron 10 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1327-1006A>G		intron_variant	Intron 10 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000525707.2	n.126-1006A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88790 AN: 152006 Hom.: 28508 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.584 AC: 88891 AN: 152124 Hom.: 28556 Cov.: 32 AF XY: 0.576 AC XY: 42823 AN XY: 74348

African (AFR) AF: 0.845 AC: 35073 AN: 41520

American (AMR) AF: 0.562 AC: 8589 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3468

East Asian (EAS) AF: 0.787 AC: 4079 AN: 5184

South Asian (SAS) AF: 0.537 AC: 2588 AN: 4818

European-Finnish (FIN) AF: 0.316 AC: 3342 AN: 10574

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31473 AN: 67962

Other (OTH) AF: 0.603 AC: 1275 AN: 2114

Alfa AF: 0.544 Hom.: 3122

Bravo AF: 0.617

Asia WGS AF: 0.670 AC: 2325 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.26
PhyloP100		-0.0040
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: rs480496; hg19: chr11-34488829;