rs25685

Positions:

• chr16-4506910-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002134.4(HMOX2):​c.102G>A​(p.Ser34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 1,612,734 control chromosomes in the GnomAD database, including 2,607 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 0.081 (800 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1807 hom.)
• Consequence: HMOX2 NM_002134.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.26

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-4.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX2	NM_002134.4	c.102G>A	p.Ser34=	synonymous_variant	3/6	ENST00000570646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX2	ENST00000570646.6	c.102G>A	p.Ser34=	synonymous_variant	3/6	1	NM_002134.4	P1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12293 AN: 151972 Hom.: 798 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0154

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0720

GnomAD3 exomes AF: 0.0516 AC: 12978 AN: 251440 Hom.: 621 AF XY: 0.0449 AC XY: 6100 AN XY: 135886

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.0528

Gnomad EAS exome AF: 0.00261

Gnomad SAS exome AF: 0.0165

Gnomad FIN exome AF: 0.0252

Gnomad NFE exome AF: 0.0369

Gnomad OTH exome AF: 0.0450

GnomAD4 exome AF: 0.0409 AC: 59801 AN: 1460642 Hom.: 1807 Cov.: 30 AF XY: 0.0395 AC XY: 28702 AN XY: 726770

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.0527

Gnomad4 EAS exome AF: 0.00403

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.0373

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0809 AC: 12300 AN: 152092 Hom.: 800 Cov.: 32 AF XY: 0.0792 AC XY: 5888 AN XY: 74344

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0498

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0152

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0378

Gnomad4 OTH AF: 0.0713

Alfa AF: 0.0588 Hom.: 191

Bravo AF: 0.0921

Asia WGS AF: 0.0240 AC: 84 AN: 3478

EpiCase AF: 0.0401

EpiControl AF: 0.0375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.8
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs25685; hg19: chr16-4556911;