rs566979

Variant names:

• chr11-34469100-A-C
• rs566979
• NM_001752.4:c.1434+705A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-34469100-A-C
• chr11-34469100-A-T

Variant summary

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

The NM_001752.4(CAT):​c.1434+705A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,034 control chromosomes in the GnomAD database, including 14,973 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 0.43 (14973 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837
• Publications: 16 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1434+705A>C		intron_variant	Intron 11 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1434+705A>C		intron_variant	Intron 11 of 12	1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65351 AN: 151916 Hom.: 14952 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.430 AC: 65416 AN: 152034 Hom.: 14973 Cov.: 32 AF XY: 0.424 AC XY: 31519 AN XY: 74296

African (AFR) AF: 0.582 AC: 24152 AN: 41470

American (AMR) AF: 0.407 AC: 6225 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2440 AN: 5168

South Asian (SAS) AF: 0.487 AC: 2346 AN: 4818

European-Finnish (FIN) AF: 0.239 AC: 2528 AN: 10572

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24885 AN: 67944

Other (OTH) AF: 0.440 AC: 926 AN: 2106

Alfa AF: 0.386 Hom.: 14411

Bravo AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.49
PhyloP100		-0.84
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: rs566979; hg19: chr11-34490647;