chr11-34442192-T-C

Variant names:

• chr11-34442192-T-C
• rs4756146
• NM_001752.4:c.66+3113T>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.66+3113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,314 control chromosomes in the GnomAD database, including 1,374 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 0.12 (1374 hom., cov: 33)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.66+3113T>C		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+3113T>C		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18236 AN: 152196 Hom.: 1365 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.120 AC: 18253 AN: 152314 Hom.: 1374 Cov.: 33 AF XY: 0.124 AC XY: 9218 AN XY: 74468

African (AFR) AF: 0.0493 AC: 2051 AN: 41586

American (AMR) AF: 0.207 AC: 3171 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3472

East Asian (EAS) AF: 0.184 AC: 955 AN: 5186

South Asian (SAS) AF: 0.172 AC: 830 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10610

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8933 AN: 68026

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.123 Hom.: 479

Bravo AF: 0.123

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.92
PhyloP100		-0.22
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: rs4756146; hg19: chr11-34463739;