11-34461361-C-T

Variant names:

• chr11-34461361-C-T
• rs769217
• NM_001752.4:c.1167C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001752.4(CAT):​c.1167C>T​(p.Asp389Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,613,666 control chromosomes in the GnomAD database, including 45,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4283 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41310 hom.)
• Consequence: CAT NM_001752.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.503
• Publications: 119 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 11-34461361-C-T is Benign according to our data. Variant chr11-34461361-C-T is described in ClinVar as Benign. ClinVar VariationId is 559061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.503 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	NM_001752.4	MANE Select	c.1167C>T	p.Asp389Asp	synonymous	Exon 9 of 13	NP_001743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	ENST00000241052.5	TSL:1 MANE Select	c.1167C>T	p.Asp389Asp	synonymous	Exon 9 of 13	ENSP00000241052.4
	CAT	ENST00000530343.1	TSL:2	n.629C>T		non_coding_transcript_exon	Exon 1 of 2
	CAT	ENST00000650153.1		n.*1059C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34219 AN: 152006 Hom.: 4273 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.249 AC: 62637 AN: 251478 AF XY: 0.249

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.232 AC: 339031 AN: 1461542 Hom.: 41310 Cov.: 34 AF XY: 0.234 AC XY: 169792 AN XY: 727076

African (AFR) AF: 0.161 AC: 5404 AN: 33476

American (AMR) AF: 0.296 AC: 13236 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6349 AN: 26132

East Asian (EAS) AF: 0.452 AC: 17935 AN: 39696

South Asian (SAS) AF: 0.238 AC: 20552 AN: 86248

European-Finnish (FIN) AF: 0.203 AC: 10864 AN: 53414

Middle Eastern (MID) AF: 0.311 AC: 1796 AN: 5768

European-Non Finnish (NFE) AF: 0.223 AC: 247795 AN: 1111702

Other (OTH) AF: 0.250 AC: 15100 AN: 60384

GnomAD4 genome AF: 0.225 AC: 34254 AN: 152124 Hom.: 4283 Cov.: 32 AF XY: 0.227 AC XY: 16896 AN XY: 74368

African (AFR) AF: 0.161 AC: 6701 AN: 41494

American (AMR) AF: 0.305 AC: 4661 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2456 AN: 5162

South Asian (SAS) AF: 0.220 AC: 1063 AN: 4830

European-Finnish (FIN) AF: 0.197 AC: 2083 AN: 10572

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15448 AN: 67994

Other (OTH) AF: 0.271 AC: 574 AN: 2116

Alfa AF: 0.230 Hom.: 17408

Bravo AF: 0.234

Asia WGS AF: 0.339 AC: 1177 AN: 3478

EpiCase AF: 0.239

EpiControl AF: 0.238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs769217; hg19: chr11-34482908; COSMIC: COSV53811275; COSMIC: COSV53811275;