rs2071746

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 138 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), Ambry Genetics, Orphanet, ClinGen
• 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412893.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	ENST00000412893.5	TSL:3	c.-241+199A>T		intron	N/A	ENSP00000413316.1	B1AHA8

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

African (AFR) AF: 0.661 AC: 27358 AN: 41412

American (AMR) AF: 0.343 AC: 5237 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3468

East Asian (EAS) AF: 0.544 AC: 2790 AN: 5132

South Asian (SAS) AF: 0.533 AC: 2570 AN: 4824

European-Finnish (FIN) AF: 0.424 AC: 4462 AN: 10528

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28793 AN: 67916

Other (OTH) AF: 0.465 AC: 981 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.6
DANN	Benign	0.87
PhyloP100		0.031
PromoterAI		0.027	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2071746;

hg19: chr22-35776672;