chr11-34454241-T-C

Variant names:

• chr11-34454241-T-C
• rs1408034
• NM_001752.4:c.711+315T>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.711+315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,276 control chromosomes in the GnomAD database, including 925 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 0.10 (925 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.711+315T>C		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.711+315T>C		intron_variant	Intron 6 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000528104.2	n.81+315T>C		intron_variant	Intron 1 of 2	2
CAT	ENST00000650153.1	n.*531+315T>C		intron_variant	Intron 5 of 8			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15757 AN: 152158 Hom.: 923 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.104 AC: 15775 AN: 152276 Hom.: 925 Cov.: 32 AF XY: 0.102 AC XY: 7563 AN XY: 74462

African (AFR) AF: 0.105 AC: 4364 AN: 41564

American (AMR) AF: 0.0989 AC: 1513 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1532 AN: 5188

South Asian (SAS) AF: 0.0491 AC: 237 AN: 4822

European-Finnish (FIN) AF: 0.0730 AC: 774 AN: 10610

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.0959 AC: 6524 AN: 68006

Other (OTH) AF: 0.131 AC: 277 AN: 2114

Alfa AF: 0.0981 Hom.: 146

Bravo AF: 0.109

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.82
PhyloP100		-0.83
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: rs1408034; hg19: chr11-34475788;