chr22-35393270-A-G

Variant names:

• chr22-35393270-A-G
• rs2285112
• NM_002133.3:c.737-198A>G

Variant summary

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

The NM_002133.3(HMOX1):​c.737-198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,990 control chromosomes in the GnomAD database, including 17,810 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 0.46 (17810 hom., cov: 32)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 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.737-198A>G		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.737-198A>G		intron	N/A	ENSP00000216117.8
	HMOX1	ENST00000679074.1		c.637-198A>G		intron	N/A	ENSP00000503459.1
	HMOX1	ENST00000678411.1		c.344-198A>G		intron	N/A	ENSP00000503526.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70560 AN: 151874 Hom.: 17789 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.465 AC: 70623 AN: 151990 Hom.: 17810 Cov.: 32 AF XY: 0.463 AC XY: 34408 AN XY: 74298

African (AFR) AF: 0.675 AC: 28001 AN: 41454

American (AMR) AF: 0.320 AC: 4880 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3472

East Asian (EAS) AF: 0.491 AC: 2532 AN: 5152

South Asian (SAS) AF: 0.510 AC: 2457 AN: 4818

European-Finnish (FIN) AF: 0.384 AC: 4051 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25862 AN: 67958

Other (OTH) AF: 0.448 AC: 946 AN: 2112

Alfa AF: 0.408 Hom.: 20686

Bravo AF: 0.467

Asia WGS AF: 0.537 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.81
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs2285112; hg19: chr22-35789263; COSMIC: COSV53340942; COSMIC: COSV53340942;