16-4496585-G-C

Position:

• chr16-4496585-G-C

Variant summary

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

The NM_002134.4(HMOX2):​c.-41-8899G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,084 control chromosomes in the GnomAD database, including 25,541 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 0.54 (25538 hom., cov: 31)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

HMOX2 (HGNC:5014): (heme oxygenase 2) 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. Several alternatively spliced transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

HMOX2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.-41-8899G>C		intron_variant		ENST00000570646.6	NP_002125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX2	ENST00000570646.6	c.-41-8899G>C		intron_variant		1	NM_002134.4	ENSP00000459214.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82147 AN: 151958 Hom.: 25530 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.875 AC XY: 7 AN XY: 8

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.833

GnomAD4 genome AF: 0.540 AC: 82167 AN: 152076 Hom.: 25538 Cov.: 31 AF XY: 0.540 AC XY: 40173 AN XY: 74354

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.563

Alfa AF: 0.614 Hom.: 3918

Bravo AF: 0.515

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.67

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: rs3789038; hg19: chr16-4546586;