NM_002133.3:c.19G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002133.3(HMOX1):c.19G>C(p.Asp7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,547,162 control chromosomes in the GnomAD database, including 2,219 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D7E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.042 ( 161 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2058 hom. )

Consequence

HMOX1
NM_002133.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.311

Publications

57 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002096802).

BP6

Variant 22-35381192-G-C is Benign according to our data. Variant chr22-35381192-G-C is described in ClinVar as Benign. ClinVar VariationId is 1168542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3 link	c.19G>C	p.Asp7His	missense_variant	Exon 1 of 5	ENST00000216117.9	NP_002124.1	P09601Q6FH11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9 link	c.19G>C	p.Asp7His	missense_variant	Exon 1 of 5	1	NM_002133.3	ENSP00000216117.8		P09601

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6317

AN:

152214

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0340

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.0586

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0494

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0534

Gnomad OTH

AF:

0.0420

GnomAD2 exomes

AF:

0.0429

AC:

6202

AN:

144592

AF XY:

0.0419

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.0422

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.0529

Gnomad FIN exome

AF:

0.0492

Gnomad NFE exome

AF:

0.0543

Gnomad OTH exome

AF:

0.0407

GnomAD4 exome

AF:

0.0519

AC:

72432

AN:

1394830

Hom.:

2058

Cov.:

AF XY:

0.0513

AC XY:

35375

AN XY:

689346

show subpopulations

African (AFR)

AF:

0.0218

AC:

703

AN:

32226

American (AMR)

AF:

0.0421

AC:

1540

AN:

36576

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

569

AN:

25236

East Asian (EAS)

AF:

0.0721

AC:

2641

AN:

36614

South Asian (SAS)

AF:

0.0245

AC:

1962

AN:

80004

European-Finnish (FIN)

AF:

0.0470

AC:

1678

AN:

35696

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0559

AC:

60575

AN:

1084516

Other (OTH)

AF:

0.0461

AC:

2685

AN:

58262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3788

7576

11364

15152

18940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2300

4600

6900

9200

11500

<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:

0.0415

AC:

6326

AN:

152332

Hom.:

161

Cov.:

AF XY:

0.0411

AC XY:

3059

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0243

AC:

1012

AN:

41578

American (AMR)

AF:

0.0342

AC:

524

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3470

East Asian (EAS)

AF:

0.0581

AC:

301

AN:

5178

South Asian (SAS)

AF:

0.0224

AC:

108

AN:

4832

European-Finnish (FIN)

AF:

0.0494

AC:

525

AN:

10624

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0534

AC:

3631

AN:

68024

Other (OTH)

AF:

0.0411

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

317

634

952

1269

1586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0336

Hom.:

Bravo

AF:

0.0404

TwinsUK

AF:

0.0539

AC:

200

ALSPAC

AF:

0.0555

AC:

214

ESP6500AA

AF:

0.0162

AC:

ESP6500EA

AF:

0.0367

AC:

276

ExAC

AF:

0.0314

AC:

3393

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

.;N

PhyloP100

0.31

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.0010

.;B

Vest4

0.059

MPC

0.061

ClinPred

0.0028

GERP RS

2.4

PromoterAI

-0.047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.28

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over