rs511895

Variant names:

• chr11-34466182-T-C
• rs511895
• NM_001752.4:c.1326+1947T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001752.4(CAT):​c.1326+1947T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,166 control chromosomes in the GnomAD database, including 39,788 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 (39788 hom., cov: 33)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 27 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1326+1947T>C		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.1326+1947T>C		intron_variant	Intron 10 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000525707.2	n.125+1947T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107266 AN: 152048 Hom.: 39720 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.706 AC: 107391 AN: 152166 Hom.: 39788 Cov.: 33 AF XY: 0.701 AC XY: 52174 AN XY: 74386

African (AFR) AF: 0.899 AC: 37355 AN: 41552

American (AMR) AF: 0.769 AC: 11764 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2452 AN: 3472

East Asian (EAS) AF: 0.970 AC: 5030 AN: 5188

South Asian (SAS) AF: 0.709 AC: 3421 AN: 4828

European-Finnish (FIN) AF: 0.441 AC: 4651 AN: 10554

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40405 AN: 67958

Other (OTH) AF: 0.746 AC: 1577 AN: 2114

Alfa AF: 0.640 Hom.: 52880

Bravo AF: 0.742

Asia WGS AF: 0.851 AC: 2959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		-0.27
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: rs511895; hg19: chr11-34487729;