rs2071748

Variant names:

• chr22-35381625-G-A
• rs2071748
• NM_002133.3:c.23+429G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-35381625-G-A
• chr22-35381625-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002133.3(HMOX1):​c.23+429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,844 control chromosomes in the GnomAD database, including 15,966 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 0.44 (15966 hom., cov: 30)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.12
• Publications: 20 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), ClinGen, Ambry Genetics, Orphanet
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.23+429G>A		intron_variant	Intron 1 of 4	ENST00000216117.9	NP_002124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9	c.23+429G>A		intron_variant	Intron 1 of 4	1	NM_002133.3	ENSP00000216117.8

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67224 AN: 151726 Hom.: 15954 Cov.: 30

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.443 AC: 67277 AN: 151844 Hom.: 15966 Cov.: 30 AF XY: 0.442 AC XY: 32815 AN XY: 74164

African (AFR) AF: 0.624 AC: 25825 AN: 41398

American (AMR) AF: 0.308 AC: 4699 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2569 AN: 5154

South Asian (SAS) AF: 0.510 AC: 2445 AN: 4798

European-Finnish (FIN) AF: 0.375 AC: 3948 AN: 10520

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25159 AN: 67942

Other (OTH) AF: 0.422 AC: 887 AN: 2102

Alfa AF: 0.394 Hom.: 35866

Bravo AF: 0.444

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.59
PhyloP100		-4.1
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: rs2071748; hg19: chr22-35777618;