chr22-35387420-A-G

Variant names:

• chr22-35387420-A-G
• rs2071749
• NM_002133.3:c.636+244A>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.636+244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,162 control chromosomes in the GnomAD database, including 32,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.63 (32708 hom., cov: 33)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 37 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: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	NM_002133.3	MANE Select	c.636+244A>G		intron	N/A	NP_002124.1	Q6FH11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	ENST00000216117.9	TSL:1 MANE Select	c.636+244A>G		intron	N/A	ENSP00000216117.8	P09601
	HMOX1	ENST00000679074.1		c.636+244A>G		intron	N/A	ENSP00000503459.1	A0A7I2V3I1
	HMOX1	ENST00000678411.1		c.243+244A>G		intron	N/A	ENSP00000503526.1	A0A7I2V3M0

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96281 AN: 152042 Hom.: 32667 Cov.: 33

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.633 AC: 96378 AN: 152162 Hom.: 32708 Cov.: 33 AF XY: 0.633 AC XY: 47070 AN XY: 74358

African (AFR) AF: 0.896 AC: 37222 AN: 41550

American (AMR) AF: 0.458 AC: 7000 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1833 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3575 AN: 5174

South Asian (SAS) AF: 0.658 AC: 3171 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5909 AN: 10570

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35805 AN: 67974

Other (OTH) AF: 0.598 AC: 1264 AN: 2114

Alfa AF: 0.566 Hom.: 21617

Bravo AF: 0.635

Asia WGS AF: 0.723 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-0.44
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: rs2071749; hg19: chr22-35783413;