rs2071746

Variant names:

• chr22-35380679-A-T
• rs2071746
• ENST00000412893.5:c.-241+199A>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000412893.5	c.-241+199A>T		intron_variant	Intron 1 of 3	3		ENSP00000413316.1

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;