dbSNP rs1483623337: HMOX1:p.Asp7Glu (chr22-35381194-C-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.21C>A(p.Asp7Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,395,160 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in 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: 0.0000014 ( 0 hom. )

Consequence

HMOX1
NM_002133.3 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.58

Publications

2 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: 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=0.107308686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3 link	c.21C>A	p.Asp7Glu	missense_variant, splice_region_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.21C>A	p.Asp7Glu	missense_variant, splice_region_variant	Exon 1 of 5	1	NM_002133.3	ENSP00000216117.8		P09601

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000690

AC:

AN:

144850

AF XY:

0.0000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000143

AC:

AN:

1395160

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689538

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32246

American (AMR)

AF:

0.00

AC:

AN:

36622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25242

East Asian (EAS)

AF:

0.00

AC:

AN:

36650

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084670

Other (OTH)

AF:

0.00

AC:

AN:

58268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

.;N

PhyloP100

1.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.070

N;N

REVEL

Benign

0.090

Sift

Benign

0.39

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

.;B

Vest4

0.15

MutPred

0.092

Gain of solvent accessibility (P = 0.1014);Gain of solvent accessibility (P = 0.1014);

MVP

0.29

MPC

0.051

ClinPred

0.089

GERP RS

3.4

PromoterAI

0.11

Neutral

(source)

Varity_R

0.14

gMVP

0.095

Mutation Taster

=89/11

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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rs1483623337

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