rs1051308

Positions:

• chr16-4510300-G-A

Variant summary

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

The NM_002134.4(HMOX2):​c.*544G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 159,512 control chromosomes in the GnomAD database, including 27,231 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 (25777 hom., cov: 32)
  • Exomes 𝑓: 0.62 (1454 hom.)
• Consequence: HMOX2 NM_002134.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX2	NM_002134.4	c.*544G>A		3_prime_UTR_variant	6/6	ENST00000570646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX2	ENST00000570646.6	c.*544G>A		3_prime_UTR_variant	6/6	1	NM_002134.4	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82835 AN: 151922 Hom.: 25768 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.618 AC: 4617 AN: 7472 Hom.: 1454 Cov.: 0 AF XY: 0.618 AC XY: 2456 AN XY: 3976

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.631

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.545 AC: 82861 AN: 152040 Hom.: 25777 Cov.: 32 AF XY: 0.545 AC XY: 40519 AN XY: 74314

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.568

Alfa AF: 0.647 Hom.: 34164

Bravo AF: 0.520

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.56

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: rs1051308; hg19: chr16-4560301;