11-34464164-C-T

Variant names:

• chr11-34464164-C-T
• rs704724
• NM_001752.4:c.1255C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001752.4(CAT):​c.1255C>T​(p.Leu419Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00796 in 1,613,962 control chromosomes in the GnomAD database, including 757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (375 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (382 hom.)
• Consequence: CAT NM_001752.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.187
• Publications: 13 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 11-34464164-C-T is Benign according to our data. Variant chr11-34464164-C-T is described in ClinVar as Benign. ClinVar VariationId is 559062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.187 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1255C>T	p.Leu419Leu	synonymous_variant	Exon 10 of 13	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1255C>T	p.Leu419Leu	synonymous_variant	Exon 10 of 13	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000525707.2	n.54C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
CAT	ENST00000530343.1	n.717C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5895 AN: 152096 Hom.: 375 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0105 AC: 2632 AN: 251494 AF XY: 0.00770

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.00723

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00475 AC: 6945 AN: 1461748 Hom.: 382 Cov.: 31 AF XY: 0.00410 AC XY: 2985 AN XY: 727184

African (AFR) AF: 0.142 AC: 4740 AN: 33476

American (AMR) AF: 0.00834 AC: 373 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26132

East Asian (EAS) AF: 0.0161 AC: 641 AN: 39698

South Asian (SAS) AF: 0.000429 AC: 37 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.000465 AC: 517 AN: 1111900

Other (OTH) AF: 0.00967 AC: 584 AN: 60380

GnomAD4 genome AF: 0.0388 AC: 5906 AN: 152214 Hom.: 375 Cov.: 32 AF XY: 0.0377 AC XY: 2803 AN XY: 74418

African (AFR) AF: 0.135 AC: 5585 AN: 41496

American (AMR) AF: 0.0114 AC: 174 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00985 AC: 51 AN: 5180

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68020

Other (OTH) AF: 0.0241 AC: 51 AN: 2112

Alfa AF: 0.0160 Hom.: 256

Bravo AF: 0.0443

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Aug 16, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.3
DANN	Benign	0.48
PhyloP100		0.19
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: rs704724; hg19: chr11-34485711;