rs1051308

Variant names:

• chr16-4510300-G-A
• rs1051308
• NM_002134.4:c.*544G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002134.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	NM_002134.4	MANE Select	c.*544G>A		3_prime_UTR	Exon 6 of 6	NP_002125.3
	HMOX2	NM_001286267.2		c.*544G>A		3_prime_UTR	Exon 7 of 7	NP_001273196.1
	HMOX2	NM_001127204.2		c.*544G>A		3_prime_UTR	Exon 7 of 7	NP_001120676.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	ENST00000570646.6	TSL:1 MANE Select	c.*544G>A		3_prime_UTR	Exon 6 of 6	ENSP00000459214.1
	HMOX2	ENST00000613539.1	TSL:5	c.*544G>A		3_prime_UTR	Exon 6 of 6	ENSP00000477572.1
	HMOX2	ENST00000219700.10	TSL:5	c.*544G>A		3_prime_UTR	Exon 6 of 6	ENSP00000219700.6

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

African (AFR) AF: 0.256 AC: 43 AN: 168

American (AMR) AF: 0.504 AC: 363 AN: 720

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 114 AN: 166

East Asian (EAS) AF: 0.631 AC: 279 AN: 442

South Asian (SAS) AF: 0.484 AC: 152 AN: 314

European-Finnish (FIN) AF: 0.661 AC: 271 AN: 410

Middle Eastern (MID) AF: 0.500 AC: 4 AN: 8

European-Non Finnish (NFE) AF: 0.652 AC: 3198 AN: 4906

Other (OTH) AF: 0.571 AC: 193 AN: 338

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

African (AFR) AF: 0.231 AC: 9588 AN: 41456

American (AMR) AF: 0.552 AC: 8427 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2198 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3339 AN: 5168

South Asian (SAS) AF: 0.540 AC: 2604 AN: 4824

European-Finnish (FIN) AF: 0.729 AC: 7706 AN: 10574

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47229 AN: 67968

Other (OTH) AF: 0.568 AC: 1198 AN: 2110

Alfa AF: 0.602 Hom.: 47030

Bravo AF: 0.520

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051308; hg19: chr16-4560301;