rs7943316

Positions:

• chr11-34438925-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 11-34438925-A-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,178,738 control chromosomes in the GnomAD database, including 236,522 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 0.57 (25476 hom., cov: 33)
  • Exomes 𝑓: 0.64 (211046 hom.)
• Consequence: CAT NM_001752.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAT	NM_001752.4			upstream_gene_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5			upstream_gene_variant		1	NM_001752.4	ENSP00000241052	P1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86025 AN: 151930 Hom.: 25462 Cov.: 33

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.636 AC: 652535 AN: 1026688 Hom.: 211046 Cov.: 14 AF XY: 0.636 AC XY: 331698 AN XY: 521190

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.682

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.609

GnomAD4 genome AF: 0.566 AC: 86072 AN: 152050 Hom.: 25476 Cov.: 33 AF XY: 0.563 AC XY: 41819 AN XY: 74328

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.555

Alfa AF: 0.607 Hom.: 3562

Bravo AF: 0.547

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs7943316; hg19: chr11-34460472; COSMIC: COSV53811112;