22-35385214-T-C

Variant names:

• chr22-35385214-T-C
• rs9607267
• NM_002133.3:c.145-1471T>C

Variant summary

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

The NM_002133.3(HMOX1):​c.145-1471T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,892 control chromosomes in the GnomAD database, including 6,360 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 0.28 (6360 hom., cov: 30)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.145-1471T>C		intron_variant	Intron 2 of 4	ENST00000216117.9	NP_002124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9	c.145-1471T>C		intron_variant	Intron 2 of 4	1	NM_002133.3	ENSP00000216117.8

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42290 AN: 151774 Hom.: 6370 Cov.: 30

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.278 AC: 42279 AN: 151892 Hom.: 6360 Cov.: 30 AF XY: 0.284 AC XY: 21070 AN XY: 74228

African (AFR) AF: 0.172 AC: 7129 AN: 41432

American (AMR) AF: 0.216 AC: 3300 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3466

East Asian (EAS) AF: 0.459 AC: 2362 AN: 5144

South Asian (SAS) AF: 0.410 AC: 1971 AN: 4802

European-Finnish (FIN) AF: 0.363 AC: 3828 AN: 10548

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21621 AN: 67928

Other (OTH) AF: 0.286 AC: 603 AN: 2106

Alfa AF: 0.277 Hom.: 1965

Bravo AF: 0.261

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.49
PhyloP100		-0.37
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: rs9607267; hg19: chr22-35781207;