chr11-34439157-C-G

Variant names:

• chr11-34439157-C-G
• rs10836235
• NM_001752.4:c.66+78C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001752.4(CAT):​c.66+78C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,212,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 27 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.66+78C>G		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.66+78C>G		intron_variant	Intron 1 of 12	1	NM_001752.4	ENSP00000241052.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000247 AC: 30 AN: 1212838 Hom.: 0 AF XY: 0.0000280 AC XY: 17 AN XY: 606174

African (AFR) AF: 0.00 AC: 0 AN: 27886

American (AMR) AF: 0.00 AC: 0 AN: 35482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23952

East Asian (EAS) AF: 0.00 AC: 0 AN: 34878

South Asian (SAS) AF: 0.00 AC: 0 AN: 75570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.0000319 AC: 29 AN: 910416

Other (OTH) AF: 0.0000193 AC: 1 AN: 51816

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1050

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-2.7
PromoterAI		-0.013	Neutral

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: rs10836235; hg19: chr11-34460704;