11-34453135-C-A

Variant names:

• chr11-34453135-C-A
• rs148174786
• NM_001752.4:c.526C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001752.4(CAT):​c.526C>A​(p.Leu176Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,613,610 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: CAT NM_001752.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015075684).
• BP6: Variant 11-34453135-C-A is Benign according to our data. Variant chr11-34453135-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 707827.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.526C>A	p.Leu176Met	missense_variant	Exon 5 of 13	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.526C>A	p.Leu176Met	missense_variant	Exon 5 of 13	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000650153.1	n.*346C>A		non_coding_transcript_exon_variant	Exon 4 of 9			ENSP00000497751.1
CAT	ENST00000650153.1	n.*346C>A		3_prime_UTR_variant	Exon 4 of 9			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.000887 AC: 135 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000213 AC: 53 AN: 248556 AF XY: 0.000111

Gnomad AFR exome AF: 0.00253

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 147 AN: 1461272 Hom.: 0 Cov.: 29 AF XY: 0.0000894 AC XY: 65 AN XY: 726992

African (AFR) AF: 0.00326 AC: 109 AN: 33456

American (AMR) AF: 0.000380 AC: 17 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111498

Other (OTH) AF: 0.000199 AC: 12 AN: 60368

GnomAD4 genome AF: 0.000906 AC: 138 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.000980 AC XY: 73 AN XY: 74490

African (AFR) AF: 0.00313 AC: 130 AN: 41572

American (AMR) AF: 0.000457 AC: 7 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000293 Hom.: 0

Bravo AF: 0.000971

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000231 AC: 28

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.015	T;T
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.5	L;L
PhyloP100		1.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N;.
REVEL	Pathogenic	0.67
Sift	Benign	0.061	T;.
Sift4G	Benign	0.19	T;.
Polyphen		0.74	P;P
Vest4		0.40
MVP		0.94
MPC		0.41
ClinPred		0.065	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.54
Mutation Taster		=74/26	polymorphism

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: rs148174786; hg19: chr11-34474682;