NM_001752.4:c.67-3593A>C

Variant names:

• chr11-34445599-A-C
• rs2179625
• NM_001752.4:c.67-3593A>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.67-3593A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,078 control chromosomes in the GnomAD database, including 3,759 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 0.21 (3759 hom., cov: 28)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 6 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001752.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	NM_001752.4	MANE Select	c.67-3593A>C		intron	N/A	NP_001743.1	P04040

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	ENST00000241052.5	TSL:1 MANE Select	c.67-3593A>C		intron	N/A	ENSP00000241052.4	P04040
	CAT	ENST00000955133.1		c.67-3593A>C		intron	N/A	ENSP00000625192.1
	CAT	ENST00000955131.1		c.67-3593A>C		intron	N/A	ENSP00000625190.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31569 AN: 150978 Hom.: 3760 Cov.: 28

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.209 AC: 31567 AN: 151078 Hom.: 3759 Cov.: 28 AF XY: 0.206 AC XY: 15187 AN XY: 73770

African (AFR) AF: 0.115 AC: 4731 AN: 41078

American (AMR) AF: 0.248 AC: 3760 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1034 AN: 3462

East Asian (EAS) AF: 0.241 AC: 1241 AN: 5148

South Asian (SAS) AF: 0.337 AC: 1604 AN: 4766

European-Finnish (FIN) AF: 0.107 AC: 1107 AN: 10356

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

European-Non Finnish (NFE) AF: 0.256 AC: 17372 AN: 67816

Other (OTH) AF: 0.246 AC: 514 AN: 2092

Alfa AF: 0.245 Hom.: 6083

Bravo AF: 0.215

Asia WGS AF: 0.270 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-0.36
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: rs2179625; hg19: chr11-34467146;