rs11912889

Variant names:

• chr22-35387624-G-A
• rs11912889
• NM_002133.3:c.636+448G>A

Variant summary

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

The ENST00000216117.9(HMOX1):​c.636+448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,226 control chromosomes in the GnomAD database, including 3,959 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 0.16 (3959 hom., cov: 33)
• Consequence: HMOX1 ENST00000216117.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 13 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

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.636+448G>A		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.636+448G>A		intron	N/A	ENSP00000216117.8
	HMOX1	ENST00000679074.1		c.636+448G>A		intron	N/A	ENSP00000503459.1
	HMOX1	ENST00000678411.1		c.243+448G>A		intron	N/A	ENSP00000503526.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23842 AN: 152108 Hom.: 3954 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.157 AC: 23889 AN: 152226 Hom.: 3959 Cov.: 33 AF XY: 0.151 AC XY: 11242 AN XY: 74434

African (AFR) AF: 0.423 AC: 17574 AN: 41498

American (AMR) AF: 0.0885 AC: 1353 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3468

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5188

South Asian (SAS) AF: 0.0938 AC: 453 AN: 4828

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10620

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3601 AN: 68014

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.0818 Hom.: 611

Bravo AF: 0.174

Asia WGS AF: 0.0950 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.4
DANN	Benign	0.84
PhyloP100		0.38
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: rs11912889; hg19: chr22-35783617;