dbSNP rs58433947: HMOX1:c.-240-82_-240-69delTGTGTGTGTGTGTA (chr22-35380851-GTGTGTGTGTGTGTA-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000412893.5(HMOX1):c.-240-82_-240-69delTGTGTGTGTGTGTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 363,976 control chromosomes in the GnomAD database, including 4,029 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2038 hom., cov: 0)

Exomes 𝑓: 0.15 ( 1991 hom. )

Consequence

HMOX1
ENST00000412893.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.851

Publications

1 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)

HMOX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3 link	c.-322_-309delTGTGTGTGTGTGTA		upstream_gene_variant		ENST00000216117.9	NP_002124.1	P09601Q6FH11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9 link	c.-322_-309delTGTGTGTGTGTGTA		upstream_gene_variant		1	NM_002133.3	ENSP00000216117.8		P09601

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

23840

AN:

139770

Hom.:

2044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.233

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.150

AC:

33594

AN:

224092

Hom.:

1991

AF XY:

0.156

AC XY:

18410

AN XY:

118076

show subpopulations

African (AFR)

AF:

0.0692

AC:

274

AN:

3958

American (AMR)

AF:

0.0837

AC:

804

AN:

9610

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

1087

AN:

6364

East Asian (EAS)

AF:

0.163

AC:

1760

AN:

10770

South Asian (SAS)

AF:

0.215

AC:

5404

AN:

25178

European-Finnish (FIN)

AF:

0.132

AC:

2043

AN:

15436

Middle Eastern (MID)

AF:

0.147

AC:

144

AN:

982

European-Non Finnish (NFE)

AF:

0.146

AC:

20303

AN:

138802

Other (OTH)

AF:

0.137

AC:

1775

AN:

12992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

933

1865

2798

3730

4663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.170

AC:

23828

AN:

139884

Hom.:

2038

Cov.:

AF XY:

0.170

AC XY:

11526

AN XY:

67898

show subpopulations

African (AFR)

AF:

0.0904

AC:

3382

AN:

37426

American (AMR)

AF:

0.133

AC:

1885

AN:

14158

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

773

AN:

3250

East Asian (EAS)

AF:

0.233

AC:

996

AN:

4276

South Asian (SAS)

AF:

0.280

AC:

1210

AN:

4326

European-Finnish (FIN)

AF:

0.167

AC:

1583

AN:

9482

Middle Eastern (MID)

AF:

0.214

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.210

AC:

13432

AN:

63894

Other (OTH)

AF:

0.175

AC:

335

AN:

1916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

826

1652

2479

3305

4131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.149

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.85

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over