chr16-4496585-G-C

Variant names:

• chr16-4496585-G-C
• rs3789038
• NM_002134.4:c.-41-8899G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002134.4(HMOX2):​c.-41-8899G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,084 control chromosomes in the GnomAD database, including 25,541 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 (25538 hom., cov: 31)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 13 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 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.-41-8899G>C		intron	N/A	NP_002125.3
	HMOX2	NM_001286267.2		c.121+319G>C		intron	N/A	NP_001273196.1
	HMOX2	NM_001127204.2		c.-41-8899G>C		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.-41-8899G>C		intron	N/A	ENSP00000459214.1
	HMOX2	ENST00000574594.5	TSL:5	n.732G>C		non_coding_transcript_exon	Exon 4 of 4
	HMOX2	ENST00000613539.1	TSL:5	c.121+319G>C		intron	N/A	ENSP00000477572.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82147 AN: 151958 Hom.: 25530 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.875 AC XY: 7 AN XY: 8

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.540 AC: 82167 AN: 152076 Hom.: 25538 Cov.: 31 AF XY: 0.540 AC XY: 40173 AN XY: 74354

African (AFR) AF: 0.218 AC: 9057 AN: 41466

American (AMR) AF: 0.550 AC: 8398 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2144 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3322 AN: 5176

South Asian (SAS) AF: 0.542 AC: 2612 AN: 4820

European-Finnish (FIN) AF: 0.730 AC: 7710 AN: 10566

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47167 AN: 67984

Other (OTH) AF: 0.563 AC: 1188 AN: 2110

Alfa AF: 0.614 Hom.: 3918

Bravo AF: 0.515

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	-0.83
CADD	Benign	8.0
DANN	Benign	0.67
PhyloP100		1.9
PromoterAI		-0.022	Neutral
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: rs3789038; hg19: chr16-4546586;