11-34439157-C-T

Variant names:

• chr11-34439157-C-T
• rs10836235
• NM_001752.4:c.66+78C>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.66+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,364,252 control chromosomes in the GnomAD database, including 7,693 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 (875 hom., cov: 33)
  • Exomes 𝑓: 0.097 (6818 hom.)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 27 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.66+78C>T		intron_variant	Intron 1 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.66+78C>T		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15356 AN: 152160 Hom.: 875 Cov.: 33

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0731

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0967 AC: 117211 AN: 1211974 Hom.: 6818 AF XY: 0.0957 AC XY: 58003 AN XY: 605780

African (AFR) AF: 0.0919 AC: 2561 AN: 27870

American (AMR) AF: 0.0908 AC: 3220 AN: 35480

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 2947 AN: 23946

East Asian (EAS) AF: 0.277 AC: 9646 AN: 34866

South Asian (SAS) AF: 0.0507 AC: 3829 AN: 75564

European-Finnish (FIN) AF: 0.0769 AC: 3680 AN: 47884

Middle Eastern (MID) AF: 0.164 AC: 812 AN: 4942

European-Non Finnish (NFE) AF: 0.0929 AC: 84524 AN: 909640

Other (OTH) AF: 0.116 AC: 5992 AN: 51782

GnomAD4 genome AF: 0.101 AC: 15359 AN: 152278 Hom.: 875 Cov.: 33 AF XY: 0.0991 AC XY: 7380 AN XY: 74470

African (AFR) AF: 0.0937 AC: 3893 AN: 41568

American (AMR) AF: 0.0993 AC: 1519 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1515 AN: 5158

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4822

European-Finnish (FIN) AF: 0.0731 AC: 777 AN: 10624

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.0974 AC: 6625 AN: 68010

Other (OTH) AF: 0.126 AC: 267 AN: 2116

Alfa AF: 0.0999 Hom.: 1050

Bravo AF: 0.106

Asia WGS AF: 0.159 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-2.7
PromoterAI		-0.047	Neutral
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: rs10836235; hg19: chr11-34460704; COSMIC: COSV53812860;