rs58433947

Positions:

• chr22-35380851-GTGTGTGTGTGTGTA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000412893.5(HMOX1):​c.-240-69_-240-56del 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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000412893.5	c.-240-69_-240-56del		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 23840 AN: 139770 Hom.: 2044 Cov.: 0

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

Gnomad4 AFR exome AF: 0.0692

Gnomad4 AMR exome AF: 0.0837

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.170 AC: 23828 AN: 139884 Hom.: 2038 Cov.: 0 AF XY: 0.170 AC XY: 11526 AN XY: 67898

Gnomad4 AFR AF: 0.0904

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.175

Alfa AF: 0.149 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58433947; hg19: chr22-35776844;