rs769218

Variant names:

• chr11-34449132-G-A
• rs769218
• NM_001752.4:c.67-60G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-34449132-G-A
• chr11-34449132-G-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.67-60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,387,350 control chromosomes in the GnomAD database, including 40,013 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 0.22 (4266 hom., cov: 33)
  • Exomes 𝑓: 0.23 (35747 hom.)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• Publications: 25 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.67-60G>A		intron_variant	Intron 1 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.67-60G>A		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000650153.1	n.-150G>A		upstream_gene_variant				ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34074 AN: 152048 Hom.: 4253 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.233 AC: 288074 AN: 1235184 Hom.: 35747 AF XY: 0.235 AC XY: 146978 AN XY: 625770

African (AFR) AF: 0.156 AC: 4537 AN: 29050

American (AMR) AF: 0.297 AC: 13076 AN: 44074

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6004 AN: 24750

East Asian (EAS) AF: 0.452 AC: 17463 AN: 38630

South Asian (SAS) AF: 0.239 AC: 19508 AN: 81518

European-Finnish (FIN) AF: 0.204 AC: 10801 AN: 53072

Middle Eastern (MID) AF: 0.314 AC: 1431 AN: 4554

European-Non Finnish (NFE) AF: 0.223 AC: 202080 AN: 906864

Other (OTH) AF: 0.250 AC: 13174 AN: 52672

GnomAD4 genome AF: 0.224 AC: 34121 AN: 152166 Hom.: 4266 Cov.: 33 AF XY: 0.226 AC XY: 16822 AN XY: 74384

African (AFR) AF: 0.158 AC: 6560 AN: 41538

American (AMR) AF: 0.305 AC: 4665 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3468

East Asian (EAS) AF: 0.479 AC: 2470 AN: 5158

South Asian (SAS) AF: 0.221 AC: 1069 AN: 4832

European-Finnish (FIN) AF: 0.197 AC: 2081 AN: 10582

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

European-Non Finnish (NFE) AF: 0.227 AC: 15441 AN: 67988

Other (OTH) AF: 0.272 AC: 573 AN: 2110

Alfa AF: 0.220 Hom.: 4649

Bravo AF: 0.233

Asia WGS AF: 0.346 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.029
DANN	Benign	0.36
PhyloP100		-2.2
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: rs769218; hg19: chr11-34470679; COSMIC: COSV53811266;