NM_001752.4:c.1518+159T>C

Variant names:

• chr11-34471200-T-C
• rs12803540
• NM_001752.4:c.1518+159T>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.1518+159T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,242 control chromosomes in the GnomAD database, including 1,059 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 0.11 (1059 hom., cov: 33)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1518+159T>C		intron_variant	Intron 12 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1518+159T>C		intron_variant	Intron 12 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000534710.2	n.328+159T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16822 AN: 152124 Hom.: 1056 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.111 AC: 16846 AN: 152242 Hom.: 1059 Cov.: 33 AF XY: 0.108 AC XY: 8070 AN XY: 74444

African (AFR) AF: 0.134 AC: 5575 AN: 41522

American (AMR) AF: 0.0992 AC: 1518 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1527 AN: 5182

South Asian (SAS) AF: 0.0472 AC: 228 AN: 4832

European-Finnish (FIN) AF: 0.0665 AC: 705 AN: 10606

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6458 AN: 68008

Other (OTH) AF: 0.134 AC: 282 AN: 2112

Alfa AF: 0.105 Hom.: 149

Bravo AF: 0.118

Asia WGS AF: 0.161 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.7
DANN	Benign	0.44
PhyloP100		-0.32
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: rs12803540; hg19: chr11-34492747; COSMIC: COSV53810666; COSMIC: COSV53810666;