rs5995097

chr22-35382968-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002133.3(HMOX1):c.24-138A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 1,234,270 control chromosomes in the GnomAD database, including 1,718 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 0.042 (164 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1554 hom.)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX1	NM_002133.3	c.24-138A>C		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.24-138A>C		intron_variant		1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6324 AN: 152208 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0505 AC: 54645 AN: 1081944 Hom.: 1554 AF XY: 0.0496 AC XY: 27309 AN XY: 550366

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.0433

Gnomad4 ASJ exome AF: 0.0216

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0246

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.0552

Gnomad4 OTH exome AF: 0.0467

GnomAD4 genome AF: 0.0416 AC: 6337 AN: 152326 Hom.: 164 Cov.: 32 AF XY: 0.0411 AC XY: 3064 AN XY: 74496

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.0344

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0494

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0487 Hom.: 34

Bravo AF: 0.0406

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.83

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: rs5995097; hg19: chr22-35778961;