rs10488736

Variant names:

• chr11-34467705-C-T
• rs10488736
• NM_001752.4:c.1327-583C>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.1327-583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,786 control chromosomes in the GnomAD database, including 9,895 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 0.35 (9895 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 20 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1327-583C>T		intron_variant	Intron 10 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1327-583C>T		intron_variant	Intron 10 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000525707.2	n.126-583C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52377 AN: 151668 Hom.: 9887 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.345 AC: 52424 AN: 151786 Hom.: 9895 Cov.: 32 AF XY: 0.337 AC XY: 24999 AN XY: 74206

African (AFR) AF: 0.489 AC: 20244 AN: 41434

American (AMR) AF: 0.318 AC: 4856 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1245 AN: 5182

South Asian (SAS) AF: 0.364 AC: 1755 AN: 4822

European-Finnish (FIN) AF: 0.129 AC: 1365 AN: 10548

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20556 AN: 67760

Other (OTH) AF: 0.364 AC: 766 AN: 2106

Alfa AF: 0.324 Hom.: 11792

Bravo AF: 0.364

Asia WGS AF: 0.303 AC: 1056 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		-0.19
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: rs10488736; hg19: chr11-34489252;