rs8139532

chr22-35383575-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	UniProt
HMOX1	NM_002133.3	c.144+349G>A		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.144+349G>A		intron_variant		1	NM_002133.3	P1

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

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.0878

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0932

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0529

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0880 Hom.: 311

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs8139532; hg19: chr22-35779568;