rs2071746

Positions:

• chr22-35380679-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000412893.5(HMOX1):​c.-241+199A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,854 control chromosomes in the GnomAD database, including 19,013 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 0.49 (19013 hom., cov: 31)
• Consequence: HMOX1 ENST00000412893.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000412893.5	c.-241+199A>T		intron_variant		3		ENSP00000413316

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74008 AN: 151736 Hom.: 18993 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.488 AC: 74074 AN: 151854 Hom.: 19013 Cov.: 31 AF XY: 0.486 AC XY: 36089 AN XY: 74204

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.465

Alfa AF: 0.463 Hom.: 2388

Bravo AF: 0.488

Asia WGS AF: 0.562 AC: 1960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.6
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2071746; hg19: chr22-35776672;