22-35390233-T-C

Variant names:

• chr22-35390233-T-C
• rs2269534
• NM_002133.3:c.736+270T>C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.736+270T>C		intron_variant	Intron 4 of 4	ENST00000216117.9	NP_002124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9	c.736+270T>C		intron_variant	Intron 4 of 4	1	NM_002133.3	ENSP00000216117.8

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

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.344

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

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.291

Alfa AF: 0.289 Hom.: 779

Bravo AF: 0.265

Asia WGS AF: 0.429 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.084

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

Publications

LitVar

Other links and lift over

dbSNP: rs2269534; hg19: chr22-35786226;