11-34463426-T-C

Variant names:

• chr11-34463426-T-C
• rs2284365
• NM_001752.4:c.1196-679T>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.1196-679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,052 control chromosomes in the GnomAD database, including 5,892 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 0.27 (5892 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• Publications: 11 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), Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 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.1196-679T>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.1196-679T>C		intron	N/A	ENSP00000241052.4	P04040
	CAT	ENST00000955133.1		c.1307-679T>C		intron	N/A	ENSP00000625192.1
	CAT	ENST00000955131.1		c.1217-679T>C		intron	N/A	ENSP00000625190.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40890 AN: 151934 Hom.: 5878 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.269 AC: 40945 AN: 152052 Hom.: 5892 Cov.: 32 AF XY: 0.270 AC XY: 20079 AN XY: 74332

African (AFR) AF: 0.314 AC: 13028 AN: 41456

American (AMR) AF: 0.318 AC: 4854 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3472

East Asian (EAS) AF: 0.487 AC: 2521 AN: 5176

South Asian (SAS) AF: 0.221 AC: 1068 AN: 4826

European-Finnish (FIN) AF: 0.196 AC: 2077 AN: 10574

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15501 AN: 67978

Other (OTH) AF: 0.298 AC: 628 AN: 2104

Alfa AF: 0.248 Hom.: 13304

Bravo AF: 0.285

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.14
DANN	Benign	0.32
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2284365;

hg19: chr11-34484973;