chr22-35390233-T-C

Variant names:

• chr22-35390233-T-C
• rs2269534
• NM_002133.3:c.736+270T>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.736+270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 461,170 control chromosomes in the GnomAD database, including 25,413 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 (6480 hom., cov: 31)
  • Exomes 𝑓: 0.35 (18933 hom.)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 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.736+270T>C		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.736+270T>C		intron	N/A	ENSP00000216117.8	P09601
	HMOX1	ENST00000679074.1		c.636+3057T>C		intron	N/A	ENSP00000503459.1	A0A7I2V3I1
	HMOX1	ENST00000678411.1		c.343+270T>C		intron	N/A	ENSP00000503526.1	A0A7I2V3M0

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42891 AN: 151772 Hom.: 6489 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.352 AC: 108872 AN: 309280 Hom.: 18933 Cov.: 0 AF XY: 0.358 AC XY: 59236 AN XY: 165412

African (AFR) AF: 0.195 AC: 1696 AN: 8686

American (AMR) AF: 0.208 AC: 2946 AN: 14134

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 3392 AN: 9100

East Asian (EAS) AF: 0.455 AC: 8833 AN: 19410

South Asian (SAS) AF: 0.419 AC: 18255 AN: 43590

European-Finnish (FIN) AF: 0.381 AC: 6190 AN: 16244

Middle Eastern (MID) AF: 0.363 AC: 450 AN: 1238

European-Non Finnish (NFE) AF: 0.341 AC: 61299 AN: 179974

Other (OTH) AF: 0.344 AC: 5811 AN: 16904

GnomAD4 genome AF: 0.282 AC: 42888 AN: 151890 Hom.: 6480 Cov.: 31 AF XY: 0.288 AC XY: 21350 AN XY: 74248

African (AFR) AF: 0.183 AC: 7597 AN: 41426

American (AMR) AF: 0.218 AC: 3329 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1195 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2353 AN: 5154

South Asian (SAS) AF: 0.411 AC: 1984 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3834 AN: 10536

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

European-Non Finnish (NFE) AF: 0.320 AC: 21711 AN: 67914

Other (OTH) AF: 0.291 AC: 614 AN: 2112

Alfa AF: 0.285 Hom.: 796

Bravo AF: 0.265

Asia WGS AF: 0.429 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.084
PhyloP100		-2.7
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: rs2269534; hg19: chr22-35786226;