NM_001752.4:c.712-1019C>T

Variant names:

• chr11-34454992-C-T
• rs2300181
• NM_001752.4:c.712-1019C>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.712-1019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 150,128 control chromosomes in the GnomAD database, including 4,140 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 (4140 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 16 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 (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.712-1019C>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.712-1019C>T		intron_variant	Intron 6 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000528104.2	n.82-1019C>T		intron_variant	Intron 1 of 2	2
CAT	ENST00000650153.1	n.*532-1019C>T		intron_variant	Intron 5 of 8			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34273 AN: 150010 Hom.: 4141 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.228 AC: 34273 AN: 150128 Hom.: 4140 Cov.: 32 AF XY: 0.224 AC XY: 16428 AN XY: 73340

African (AFR) AF: 0.179 AC: 7270 AN: 40680

American (AMR) AF: 0.254 AC: 3852 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1034 AN: 3444

East Asian (EAS) AF: 0.244 AC: 1236 AN: 5066

South Asian (SAS) AF: 0.343 AC: 1618 AN: 4722

European-Finnish (FIN) AF: 0.109 AC: 1144 AN: 10482

Middle Eastern (MID) AF: 0.280 AC: 80 AN: 286

European-Non Finnish (NFE) AF: 0.258 AC: 17372 AN: 67328

Other (OTH) AF: 0.264 AC: 545 AN: 2062

Alfa AF: 0.253 Hom.: 8234

Bravo AF: 0.234

Asia WGS AF: 0.270 AC: 943 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	0.77
DANN	Benign	0.27
PhyloP100		-0.53
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: rs2300181; hg19: chr11-34476539;