rs2269533

Positions:

• chr22-35390189-A-G
• chr22-35390189-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002133.3(HMOX1):​c.736+226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 568,774 control chromosomes in the GnomAD database, including 62,710 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 0.49 (19128 hom., cov: 32)
  • Exomes 𝑓: 0.45 (43582 hom.)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.736+226A>G		intron_variant		ENST00000216117.9	NP_002124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9	c.736+226A>G		intron_variant		1	NM_002133.3	ENSP00000216117	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74305 AN: 151792 Hom.: 19108 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.451 AC: 188185 AN: 416864 Hom.: 43582 Cov.: 2 AF XY: 0.456 AC XY: 100958 AN XY: 221246

Gnomad4 AFR exome AF: 0.664

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.490 AC: 74370 AN: 151910 Hom.: 19128 Cov.: 32 AF XY: 0.488 AC XY: 36228 AN XY: 74230

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.469

Alfa AF: 0.433 Hom.: 15682

Bravo AF: 0.489

Asia WGS AF: 0.566 AC: 1973 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.36

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

LitVar

Other links and lift over

dbSNP: rs2269533; hg19: chr22-35786182;