rs8139532

Variant names:

• chr22-35383575-G-A
• rs8139532
• NM_002133.3:c.144+349G>A

Variant summary

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

The NM_002133.3(HMOX1):​c.144+349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,146 control chromosomes in the GnomAD database, including 3,755 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 0.15 (3755 hom., cov: 31)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.144+349G>A		intron_variant	Intron 2 of 4	ENST00000216117.9	NP_002124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9	c.144+349G>A		intron_variant	Intron 2 of 4	1	NM_002133.3	ENSP00000216117.8

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23311 AN: 152028 Hom.: 3751 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.154 AC: 23357 AN: 152146 Hom.: 3755 Cov.: 31 AF XY: 0.148 AC XY: 10989 AN XY: 74406

African (AFR) AF: 0.412 AC: 17068 AN: 41442

American (AMR) AF: 0.0878 AC: 1343 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3470

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5180

South Asian (SAS) AF: 0.0932 AC: 449 AN: 4818

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10620

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3595 AN: 68008

Other (OTH) AF: 0.129 AC: 271 AN: 2106

Alfa AF: 0.0962 Hom.: 378

Bravo AF: 0.170

Asia WGS AF: 0.0940 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.61
PromoterAI		-0.036	Neutral
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: rs8139532; hg19: chr22-35779568;