22-35390189-A-T

Variant names:

• chr22-35390189-A-T
• rs2269533
• NM_002133.3:c.736+226A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000216117.9(HMOX1):​c.736+226A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMOX1 ENST00000216117.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000216117.9. 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.736+226A>T		intron	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.736+226A>T		intron	N/A	ENSP00000216117.8
	HMOX1	ENST00000494998.1	TSL:2	n.463A>T		non_coding_transcript_exon	Exon 2 of 2
	HMOX1	ENST00000679074.1		c.636+3013A>T		intron	N/A	ENSP00000503459.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 417720 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 221656

African (AFR) AF: 0.00 AC: 0 AN: 12108

American (AMR) AF: 0.00 AC: 0 AN: 20398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13068

East Asian (EAS) AF: 0.00 AC: 0 AN: 27944

South Asian (SAS) AF: 0.00 AC: 0 AN: 46958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1780

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 246596

Other (OTH) AF: 0.00 AC: 0 AN: 23756

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 29042

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.89
DANN	Benign	0.45
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs2269533; hg19: chr22-35786182;