chr11-34456170-A-G

Variant names:

• chr11-34456170-A-G
• rs56248816
• NM_001752.4:c.871A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001752.4(CAT):​c.871A>G​(p.Thr291Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: CAT NM_001752.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.87

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.009804934).
• BP6: Variant 11-34456170-A-G is Benign according to our data. Variant chr11-34456170-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 727549.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAT	NM_001752.4	c.871A>G	p.Thr291Ala	missense_variant	Exon 7 of 13	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.871A>G	p.Thr291Ala	missense_variant	Exon 7 of 13	1	NM_001752.4	ENSP00000241052.4
CAT	ENST00000528104.2	n.241A>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
CAT	ENST00000650153.1	n.*691A>G		non_coding_transcript_exon_variant	Exon 6 of 9			ENSP00000497751.1
CAT	ENST00000650153.1	n.*691A>G		3_prime_UTR_variant	Exon 6 of 9			ENSP00000497751.1

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000219 AC: 55 AN: 250782 Hom.: 1 AF XY: 0.000177 AC XY: 24 AN XY: 135686

Gnomad AFR exome AF: 0.00329

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000780 AC: 114 AN: 1461736 Hom.: 0 Cov.: 31 AF XY: 0.0000701 AC XY: 51 AN XY: 727174

Gnomad4 AFR exome AF: 0.00290

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000994

GnomAD4 genome AF: 0.000794 AC: 121 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74482

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000121 Hom.: 1

Bravo AF: 0.000820

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000255 AC: 31

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.71
DEOGEN2	Benign	0.34	T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.77
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.0098	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.40	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.38	N;.
REVEL	Benign	0.15
Sift	Benign	0.13	T;.
Sift4G	Benign	0.11	T;.
Polyphen		0.0	B;B
Vest4		0.19
MVP		0.86
MPC		0.12
ClinPred		0.0054	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.56

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: rs56248816; hg19: chr11-34477717;