rs1408034

Positions:

• chr11-34454241-T-C

Variant summary

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

The NM_001752.4(CAT):​c.711+315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,276 control chromosomes in the GnomAD database, including 925 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 (925 hom., cov: 32)
• Consequence: CAT NM_001752.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAT	NM_001752.4	c.711+315T>C		intron_variant		ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.711+315T>C		intron_variant		1	NM_001752.4	ENSP00000241052	P1
CAT	ENST00000650153.1	c.*531+315T>C		intron_variant, NMD_transcript_variant				ENSP00000497751
CAT	ENST00000528104.2	n.81+315T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15757 AN: 152158 Hom.: 923 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.104 AC: 15775 AN: 152276 Hom.: 925 Cov.: 32 AF XY: 0.102 AC XY: 7563 AN XY: 74462

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0989

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0730

Gnomad4 NFE AF: 0.0959

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0978 Hom.: 144

Bravo AF: 0.109

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.82

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: rs1408034; hg19: chr11-34475788;