11-34447092-A-T

Variant names:

• chr11-34447092-A-T
• rs560807
• NM_001752.4:c.67-2100A>T

Variant summary

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

The NM_001752.4(CAT):​c.67-2100A>T 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 152,106 control chromosomes in the GnomAD database, including 40,474 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 (40474 hom., cov: 31)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001752.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	NM_001752.4	MANE Select	c.67-2100A>T		intron	N/A	NP_001743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	ENST00000241052.5	TSL:1 MANE Select	c.67-2100A>T		intron	N/A	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107995 AN: 151988 Hom.: 40403 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.711 AC: 108123 AN: 152106 Hom.: 40474 Cov.: 31 AF XY: 0.706 AC XY: 52464 AN XY: 74342

African (AFR) AF: 0.917 AC: 38094 AN: 41520

American (AMR) AF: 0.772 AC: 11782 AN: 15266

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

East Asian (EAS) AF: 0.965 AC: 5002 AN: 5184

South Asian (SAS) AF: 0.709 AC: 3422 AN: 4828

European-Finnish (FIN) AF: 0.440 AC: 4644 AN: 10564

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40409 AN: 67958

Other (OTH) AF: 0.750 AC: 1583 AN: 2110

Alfa AF: 0.532 Hom.: 1533

Bravo AF: 0.748

Asia WGS AF: 0.852 AC: 2962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.052
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: rs560807; hg19: chr11-34468639;