rs25685

Variant names:

• chr16-4506910-G-A
• rs25685
• NM_002134.4:c.102G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002134.4(HMOX2):​c.102G>A​(p.Ser34Ser) 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
• Publications: 8 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	NM_002134.4	MANE Select	c.102G>A	p.Ser34Ser	synonymous	Exon 3 of 6	NP_002125.3
	HMOX2	NM_001286267.2		c.264G>A	p.Ser88Ser	synonymous	Exon 4 of 7	NP_001273196.1
	HMOX2	NM_001127204.2		c.102G>A	p.Ser34Ser	synonymous	Exon 4 of 7	NP_001120676.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	ENST00000570646.6	TSL:1 MANE Select	c.102G>A	p.Ser34Ser	synonymous	Exon 3 of 6	ENSP00000459214.1
	HMOX2	ENST00000613539.1	TSL:5	c.264G>A	p.Ser88Ser	synonymous	Exon 3 of 6	ENSP00000477572.1
	HMOX2	ENST00000219700.10	TSL:5	c.102G>A	p.Ser34Ser	synonymous	Exon 3 of 6	ENSP00000219700.6

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

GnomAD2 exomes AF: 0.0516 AC: 12978 AN: 251440 AF XY: 0.0449

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 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

African (AFR) AF: 0.177 AC: 5914 AN: 33408

American (AMR) AF: 0.118 AC: 5259 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 1377 AN: 26124

East Asian (EAS) AF: 0.00403 AC: 160 AN: 39696

South Asian (SAS) AF: 0.0163 AC: 1409 AN: 86256

European-Finnish (FIN) AF: 0.0260 AC: 1388 AN: 53418

Middle Eastern (MID) AF: 0.0279 AC: 161 AN: 5762

European-Non Finnish (NFE) AF: 0.0373 AC: 41388 AN: 1110900

Other (OTH) AF: 0.0455 AC: 2745 AN: 60362

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

African (AFR) AF: 0.175 AC: 7238 AN: 41458

American (AMR) AF: 0.116 AC: 1776 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 173 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0152 AC: 73 AN: 4816

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0378 AC: 2573 AN: 67982

Other (OTH) AF: 0.0713 AC: 150 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.8
DANN	Benign	0.82
PhyloP100		-4.3
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs25685; hg19: chr16-4556911;