NM_002134.4:c.-42+3125A>G

Variant names:

• chr16-4479612-A-G
• rs6500610
• NM_002134.4:c.-42+3125A>G

Variant summary

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

The NM_002134.4(HMOX2):​c.-42+3125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,924 control chromosomes in the GnomAD database, including 39,532 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 0.72 (39530 hom., cov: 30)
  • Exomes 𝑓: 0.63 (2 hom.)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 11 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]

NMRAL1 (HGNC:24987): (NmrA like redox sensor 1) This gene encodes an NADPH sensor protein that preferentially binds to NADPH. The encoded protein also negatively regulates the activity of NF-kappaB in a ubiquitylation-dependent manner. It plays a key role in cellular antiviral response by negatively regulating the interferon response factor 3-mediated expression of interferon beta. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

LOC124903636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 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.-42+3125A>G		intron	N/A	NP_002125.3
	HMOX2	NM_001286267.2		c.-1+3125A>G		intron	N/A	NP_001273196.1
	HMOX2	NM_001127204.2		c.-160+3125A>G		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.-42+3125A>G		intron	N/A	ENSP00000459214.1
	HMOX2	ENST00000219700.10	TSL:5	c.-42+3195A>G		intron	N/A	ENSP00000219700.6
	HMOX2	ENST00000406590.6	TSL:5	c.-42+4765A>G		intron	N/A	ENSP00000385100.2

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109238 AN: 151798 Hom.: 39486 Cov.: 30

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.721

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 2 AF XY: 0.833 AC XY: 5 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.720 AC: 109334 AN: 151916 Hom.: 39530 Cov.: 30 AF XY: 0.715 AC XY: 53041 AN XY: 74198

African (AFR) AF: 0.713 AC: 29527 AN: 41430

American (AMR) AF: 0.708 AC: 10785 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2475 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3321 AN: 5176

South Asian (SAS) AF: 0.558 AC: 2682 AN: 4810

European-Finnish (FIN) AF: 0.759 AC: 7985 AN: 10524

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50448 AN: 67960

Other (OTH) AF: 0.714 AC: 1506 AN: 2108

Alfa AF: 0.737 Hom.: 5142

Bravo AF: 0.719

Asia WGS AF: 0.541 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		0.44
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: rs6500610; hg19: chr16-4529613;