rs114883175

Variant names:

• chr11-34451102-A-T
• rs114883175
• NM_001752.4:c.349+4A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001752.4(CAT):​c.349+4A>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000782 in 1,566,530 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (2 hom.)
• Consequence: CAT NM_001752.4 splice_region, intron
• Scores: Splicing: ADA: 0.8740
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.30
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 11-34451102-A-T is Benign according to our data. Variant chr11-34451102-A-T is described in ClinVar as [Benign]. Clinvar id is 768441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.349+4A>T		splice_region_variant, intron_variant	Intron 3 of 12	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.349+4A>T		splice_region_variant, intron_variant	Intron 3 of 12	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000650153.1	n.*169+4A>T		splice_region_variant, intron_variant	Intron 2 of 8			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 619 AN: 152200 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00113 AC: 284 AN: 251466 AF XY: 0.000736

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000426 AC: 603 AN: 1414212 Hom.: 2 Cov.: 24 AF XY: 0.000378 AC XY: 267 AN XY: 706472

African (AFR) AF: 0.0160 AC: 519 AN: 32514

American (AMR) AF: 0.000850 AC: 38 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25864

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000525 AC: 3 AN: 5712

European-Non Finnish (NFE) AF: 0.00000374 AC: 4 AN: 1068366

Other (OTH) AF: 0.000646 AC: 38 AN: 58856

GnomAD4 genome AF: 0.00408 AC: 622 AN: 152318 Hom.: 6 Cov.: 32 AF XY: 0.00413 AC XY: 308 AN XY: 74488

African (AFR) AF: 0.0145 AC: 603 AN: 41566

American (AMR) AF: 0.000719 AC: 11 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00479

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.85
PhyloP100		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.87
dbscSNV1_RF	Pathogenic	0.73
SpliceAI score (max)		0.060		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: rs114883175; hg19: chr11-34472649;