rs12269988

Variant names:

• chr11-34451227-A-G
• rs12269988
• NM_001752.4:c.349+129A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001752.4(CAT):​c.349+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0454 in 727,814 control chromosomes in the GnomAD database, including 998 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 0.060 (337 hom., cov: 32)
  • Exomes 𝑓: 0.042 (661 hom.)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.349+129A>G		intron_variant	Intron 3 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.349+129A>G		intron_variant	Intron 3 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000650153.1	n.*169+129A>G		intron_variant	Intron 2 of 8			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9055 AN: 152198 Hom.: 337 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0416 AC: 23929 AN: 575498 Hom.: 661 AF XY: 0.0412 AC XY: 12848 AN XY: 312076

African (AFR) AF: 0.113 AC: 1826 AN: 16120

American (AMR) AF: 0.0253 AC: 891 AN: 35180

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2007 AN: 19976

East Asian (EAS) AF: 0.0000303 AC: 1 AN: 33044

South Asian (SAS) AF: 0.0275 AC: 1772 AN: 64456

European-Finnish (FIN) AF: 0.0242 AC: 1112 AN: 45942

Middle Eastern (MID) AF: 0.0689 AC: 277 AN: 4018

European-Non Finnish (NFE) AF: 0.0445 AC: 14500 AN: 325868

Other (OTH) AF: 0.0499 AC: 1543 AN: 30894

GnomAD4 genome AF: 0.0596 AC: 9080 AN: 152316 Hom.: 337 Cov.: 32 AF XY: 0.0571 AC XY: 4254 AN XY: 74490

African (AFR) AF: 0.109 AC: 4539 AN: 41552

American (AMR) AF: 0.0382 AC: 584 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 326 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0253 AC: 122 AN: 4828

European-Finnish (FIN) AF: 0.0214 AC: 227 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0455 AC: 3096 AN: 68030

Other (OTH) AF: 0.0600 AC: 127 AN: 2116

Alfa AF: 0.0501 Hom.: 300

Bravo AF: 0.0625

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.78
PhyloP100		1.6
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: rs12269988; hg19: chr11-34472774;