chr11-34455578-C-T

Variant names:

• chr11-34455578-C-T
• rs7933285
• NM_001752.4:c.712-433C>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.712-433C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 150,632 control chromosomes in the GnomAD database, including 4,143 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 0.23 (4143 hom., cov: 31)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.712-433C>T		intron_variant	Intron 6 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.712-433C>T		intron_variant	Intron 6 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000528104.2	n.82-433C>T		intron_variant	Intron 1 of 2	2
CAT	ENST00000650153.1	n.*532-433C>T		intron_variant	Intron 5 of 8			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34184 AN: 150562 Hom.: 4144 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.227 AC: 34183 AN: 150632 Hom.: 4143 Cov.: 31 AF XY: 0.223 AC XY: 16362 AN XY: 73436

African (AFR) AF: 0.177 AC: 7244 AN: 41008

American (AMR) AF: 0.254 AC: 3843 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1034 AN: 3460

East Asian (EAS) AF: 0.238 AC: 1218 AN: 5122

South Asian (SAS) AF: 0.341 AC: 1617 AN: 4744

European-Finnish (FIN) AF: 0.111 AC: 1117 AN: 10086

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17363 AN: 67766

Other (OTH) AF: 0.261 AC: 544 AN: 2086

Alfa AF: 0.261 Hom.: 8186

Bravo AF: 0.234

Asia WGS AF: 0.269 AC: 936 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.40
PhyloP100		-0.49
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: rs7933285; hg19: chr11-34477125;