GeneBe

rs866959693

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_002133.3(HMOX1):​c.23+1G>A variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HMOX1
NM_002133.3 splice_donor, intron

Scores

4
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

Publications

0 publications found
Variant links:
Genes affected
HMOX1 (HGNC:5013): (heme oxygenase 1) Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family. [provided by RefSeq, Jul 2008]
HMOX1 Gene-Disease associations (from GenCC):
  • heme oxygenase 1 deficiency
    Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
  • cystic fibrosis
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • chronic obstructive pulmonary disease
    Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMOX1NM_002133.3 linkc.23+1G>A splice_donor_variant, intron_variant Intron 1 of 4 ENST00000216117.9 NP_002124.1 P09601Q6FH11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMOX1ENST00000216117.9 linkc.23+1G>A splice_donor_variant, intron_variant Intron 1 of 4 1 NM_002133.3 ENSP00000216117.8 P09601

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1395182
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
689562
African (AFR)
AF:
0.00
AC:
0
AN:
32260
American (AMR)
AF:
0.00
AC:
0
AN:
36614
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25242
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36660
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80052
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
35718
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1084666
Other (OTH)
AF:
0.00
AC:
0
AN:
58272
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
27
DANN
Uncertain
0.99
Eigen
Pathogenic
0.84
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.98
D
PhyloP100
3.8
GERP RS
3.3
PromoterAI
-0.65
Under-expression
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=41/59
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.93
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.93
Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs866959693; hg19: chr22-35777190; API