rs2270366

Positions:

• chr16-4508614-G-A
• chr16-4508614-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.696+410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,006 control chromosomes in the GnomAD database, including 25,516 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 (25516 hom., cov: 31)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX2	NM_002134.4	c.696+410G>A		intron_variant		ENST00000570646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX2	ENST00000570646.6	c.696+410G>A		intron_variant		1	NM_002134.4	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82208 AN: 151888 Hom.: 25506 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.541 AC: 82240 AN: 152006 Hom.: 25516 Cov.: 31 AF XY: 0.541 AC XY: 40198 AN XY: 74286

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.567

Alfa AF: 0.608 Hom.: 5173

Bravo AF: 0.516

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	-0.86
CADD	Benign	5.2
DANN	Benign	0.57

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: rs2270366; hg19: chr16-4558615;