NM_002134.4:c.696+410G>A

Variant names:

• chr16-4508614-G-A
• rs2270366
• NM_002134.4:c.696+410G>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.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
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 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.696+410G>A		intron	N/A	NP_002125.3
	HMOX2	NM_001286267.2		c.858+410G>A		intron	N/A	NP_001273196.1
	HMOX2	NM_001127204.2		c.696+410G>A		intron	N/A	NP_001120676.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	ENST00000570646.6	TSL:1 MANE Select	c.696+410G>A		intron	N/A	ENSP00000459214.1
	HMOX2	ENST00000613539.1	TSL:5	c.858+410G>A		intron	N/A	ENSP00000477572.1
	HMOX2	ENST00000219700.10	TSL:5	c.696+410G>A		intron	N/A	ENSP00000219700.6

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

African (AFR) AF: 0.223 AC: 9252 AN: 41454

American (AMR) AF: 0.550 AC: 8392 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2151 AN: 3466

East Asian (EAS) AF: 0.637 AC: 3290 AN: 5166

South Asian (SAS) AF: 0.541 AC: 2603 AN: 4812

European-Finnish (FIN) AF: 0.729 AC: 7717 AN: 10584

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47073 AN: 67944

Other (OTH) AF: 0.567 AC: 1194 AN: 2106

Alfa AF: 0.631 Hom.: 9306

Bravo AF: 0.516

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.57
PhyloP100		0.26
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: rs2270366; hg19: chr16-4558615;