Genetic Variant HMOX1:p.Asp7Asn (chr22-35381192-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002133.3(HMOX1):c.19G>A(p.Asp7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,394,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D7H) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

HMOX1
NM_002133.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.095520735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3 link	c.19G>A	p.Asp7Asn	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>A	p.Asp7Asn	missense_variant	Exon 1 of 5	1	NM_002133.3	ENSP00000216117.8		P09601

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1394880

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32230

American (AMR)

AF:

0.00

AC:

AN:

36582

Ashkenazi Jewish (ASJ)

AF:

0.0000793

AC:

AN:

25236

East Asian (EAS)

AF:

0.00

AC:

AN:

36616

South Asian (SAS)

AF:

0.00

AC:

AN:

80004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35696

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084552

Other (OTH)

AF:

0.00

AC:

AN:

58264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.58

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.035

.;N

PhyloP100

0.31

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.31

N;N

REVEL

Benign

0.075

Sift

Benign

0.13

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0

.;B

Vest4

0.21

MutPred

0.098

Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);

MVP

0.28

MPC

0.053

ClinPred

0.092

GERP RS

2.4

PromoterAI

0.074

Neutral

(source)

Varity_R

0.14

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(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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chr22-35381192-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over