chr11-34462347-A-T

Variant names:

• chr11-34462347-A-T
• rs554576
• NM_001752.4:c.1195+958A>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.1195+958A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,032 control chromosomes in the GnomAD database, including 15,323 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 0.44 (15323 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.1195+958A>T		intron_variant	Intron 9 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.1195+958A>T		intron_variant	Intron 9 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000530343.1	n.657+958A>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66142 AN: 151914 Hom.: 15300 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.435 AC: 66209 AN: 152032 Hom.: 15323 Cov.: 32 AF XY: 0.430 AC XY: 31941 AN XY: 74300

African (AFR) AF: 0.583 AC: 24197 AN: 41484

American (AMR) AF: 0.450 AC: 6883 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1599 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2486 AN: 5170

South Asian (SAS) AF: 0.485 AC: 2334 AN: 4816

European-Finnish (FIN) AF: 0.242 AC: 2557 AN: 10556

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

European-Non Finnish (NFE) AF: 0.366 AC: 24895 AN: 67938

Other (OTH) AF: 0.446 AC: 942 AN: 2110

Alfa AF: 0.386 Hom.: 1688

Bravo AF: 0.457

Asia WGS AF: 0.493 AC: 1711 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.35
PhyloP100		-0.50
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: rs554576; hg19: chr11-34483894;