11-34472091-A-G

Variant names:

• chr11-34472091-A-G
• rs7104301
• NM_001752.4:c.*658A>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.*658A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,942 control chromosomes in the GnomAD database, including 4,134 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 (4115 hom., cov: 33)
  • Exomes 𝑓: 0.23 (19 hom.)
• Consequence: CAT NM_001752.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951
• Publications: 12 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 (SAS) allele frequency at 95% confidence interval = 0.323 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.*658A>G		downstream_gene	N/A	NP_001743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	ENST00000241052.5	TSL:1 MANE Select	c.*658A>G		downstream_gene	N/A	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34093 AN: 152032 Hom.: 4115 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.234 AC: 185 AN: 792 Hom.: 19 Cov.: 0 AF XY: 0.235 AC XY: 102 AN XY: 434

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.227 AC: 29 AN: 128

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.125 AC: 1 AN: 8

South Asian (SAS) AF: 0.211 AC: 16 AN: 76

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.236 AC: 130 AN: 552

Other (OTH) AF: 0.364 AC: 8 AN: 22

GnomAD4 genome AF: 0.224 AC: 34104 AN: 152150 Hom.: 4115 Cov.: 33 AF XY: 0.220 AC XY: 16338 AN XY: 74374

African (AFR) AF: 0.169 AC: 7011 AN: 41524

American (AMR) AF: 0.253 AC: 3867 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1236 AN: 5178

South Asian (SAS) AF: 0.337 AC: 1625 AN: 4820

European-Finnish (FIN) AF: 0.109 AC: 1157 AN: 10600

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17419 AN: 67970

Other (OTH) AF: 0.259 AC: 547 AN: 2108

Alfa AF: 0.257 Hom.: 6719

Bravo AF: 0.233

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.092
DANN	Benign	0.47
PhyloP100		-0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7104301; hg19: chr11-34493638;