rs17880288

Variant names:

• chr22-35394330-A-T
• rs17880288
• NM_002133.3:c.*732A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002133.3(HMOX1):​c.*732A>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 152,404 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.053 (256 hom., cov: 32)
  • Exomes 𝑓: 0.022 (1 hom.)
• Consequence: HMOX1 NM_002133.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002133.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	NM_002133.3	MANE Select	c.*732A>T		downstream_gene	N/A	NP_002124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	ENST00000216117.9	TSL:1 MANE Select	c.*732A>T		downstream_gene	N/A	ENSP00000216117.8
	HMOX1	ENST00000679074.1		c.*749A>T		downstream_gene	N/A	ENSP00000503459.1
	HMOX1	ENST00000678411.1		c.*732A>T		downstream_gene	N/A	ENSP00000503526.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8077 AN: 151254 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0443

GnomAD4 exome AF: 0.0215 AC: 23 AN: 1068 Hom.: 1 AF XY: 0.0236 AC XY: 16 AN XY: 678

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 84

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 26

South Asian (SAS) AF: 0.00 AC: 0 AN: 38

European-Finnish (FIN) AF: 0.0119 AC: 1 AN: 84

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.0269 AC: 21 AN: 782

Other (OTH) AF: 0.0294 AC: 1 AN: 34

GnomAD4 genome AF: 0.0534 AC: 8088 AN: 151336 Hom.: 256 Cov.: 32 AF XY: 0.0522 AC XY: 3855 AN XY: 73818

African (AFR) AF: 0.0682 AC: 2812 AN: 41232

American (AMR) AF: 0.0345 AC: 526 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3468

East Asian (EAS) AF: 0.00426 AC: 22 AN: 5162

South Asian (SAS) AF: 0.0264 AC: 126 AN: 4778

European-Finnish (FIN) AF: 0.0519 AC: 534 AN: 10282

Middle Eastern (MID) AF: 0.0139 AC: 4 AN: 288

European-Non Finnish (NFE) AF: 0.0565 AC: 3839 AN: 67892

Other (OTH) AF: 0.0435 AC: 91 AN: 2092

Alfa AF: 0.0590 Hom.: 39

Bravo AF: 0.0523

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.84

Splicing

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

Other links and lift over

dbSNP: rs17880288; hg19: chr22-35790323;