chr11-34453840-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001752.4(CAT):​c.625C>T​(p.His209Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,330 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 3 hom. )

Consequence

CAT
NM_001752.4 missense

Scores

3
16

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.06
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.014349788).
BP6
Variant 11-34453840-C-T is Benign according to our data. Variant chr11-34453840-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 786782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CATNM_001752.4 linkuse as main transcriptc.625C>T p.His209Tyr missense_variant 6/13 ENST00000241052.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CATENST00000241052.5 linkuse as main transcriptc.625C>T p.His209Tyr missense_variant 6/131 NM_001752.4 P1
CATENST00000650153.1 linkuse as main transcriptc.*445C>T 3_prime_UTR_variant, NMD_transcript_variant 5/9
CATENST00000528104.2 linkuse as main transcript upstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00152
AC:
231
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00509
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00215
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00184
AC:
463
AN:
251468
Hom.:
0
AF XY:
0.00194
AC XY:
264
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00453
Gnomad NFE exome
AF:
0.00302
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00205
AC:
2995
AN:
1461008
Hom.:
3
Cov.:
30
AF XY:
0.00203
AC XY:
1477
AN XY:
726882
show subpopulations
Gnomad4 AFR exome
AF:
0.000508
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.0000766
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00537
Gnomad4 NFE exome
AF:
0.00234
Gnomad4 OTH exome
AF:
0.00128
GnomAD4 genome
AF:
0.00152
AC:
231
AN:
152322
Hom.:
0
Cov.:
32
AF XY:
0.00157
AC XY:
117
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00509
Gnomad4 NFE
AF:
0.00215
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00195
Hom.:
0
Bravo
AF:
0.00131
TwinsUK
AF:
0.00243
AC:
9
ALSPAC
AF:
0.00130
AC:
5
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00174
AC:
15
ExAC
AF:
0.00222
AC:
270
EpiCase
AF:
0.00180
EpiControl
AF:
0.00190

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpNov 07, 2023Variant summary: CAT c.625C>T (p.His209Tyr) results in a conservative amino acid change located in the Catalase core domain (IPR011614) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.002 in 1613330 control chromosomes, predominantly at a frequency of 0.0023 within the Non-Finnish European subpopulation in the gnomAD database, including 3 homozygotes suggesting a benign role. To our knowledge, no occurrence of c.625C>T in individuals affected with Acatalasia and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
14
DANN
Benign
0.23
DEOGEN2
Benign
0.28
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.94
.;D
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.014
T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
-2.6
N;N
MutationTaster
Benign
0.53
N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
4.0
N;.
REVEL
Benign
0.27
Sift
Benign
1.0
T;.
Sift4G
Benign
1.0
T;.
Polyphen
0.011
B;B
Vest4
0.29
MVP
0.76
MPC
0.15
ClinPred
0.012
T
GERP RS
5.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.088
gMVP
0.86

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147148220; hg19: chr11-34475387; COSMIC: COSV99074477; COSMIC: COSV99074477; API