rs7947841

Variant names:

• chr11-34470133-G-A
• rs7947841
• NM_001752.4:c.1435-825G>A

Variant summary

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

The NM_001752.4(CAT):​c.1435-825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,128 control chromosomes in the GnomAD database, including 896 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 0.10 (896 hom., cov: 31)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 11 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	NM_001752.4	MANE Select	c.1435-825G>A		intron	N/A	NP_001743.1	P04040

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAT	ENST00000241052.5	TSL:1 MANE Select	c.1435-825G>A		intron	N/A	ENSP00000241052.4	P04040
	CAT	ENST00000955133.1		c.1546-825G>A		intron	N/A	ENSP00000625192.1
	CAT	ENST00000955131.1		c.1456-825G>A		intron	N/A	ENSP00000625190.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15552 AN: 152010 Hom.: 896 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.102 AC: 15555 AN: 152128 Hom.: 896 Cov.: 31 AF XY: 0.100 AC XY: 7469 AN XY: 74396

African (AFR) AF: 0.101 AC: 4190 AN: 41492

American (AMR) AF: 0.0961 AC: 1470 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3468

East Asian (EAS) AF: 0.294 AC: 1522 AN: 5170

South Asian (SAS) AF: 0.0488 AC: 235 AN: 4820

European-Finnish (FIN) AF: 0.0732 AC: 775 AN: 10586

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6529 AN: 67980

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.103 Hom.: 1109

Bravo AF: 0.108

Asia WGS AF: 0.159 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		1.1
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: rs7947841; hg19: chr11-34491680;