16-4479612-A-G

Position:

• chr16-4479612-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124903636 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX2	NM_002134.4	c.-42+3125A>G		intron_variant		ENST00000570646.6
LOC124903636	XR_007064964.1	n.526-51T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX2	ENST00000570646.6	c.-42+3125A>G		intron_variant		1	NM_002134.4	P1

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

Gnomad4 AMR exome AF: 0.500

Gnomad4 NFE exome AF: 0.667

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

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.714

Alfa AF: 0.740 Hom.: 4969

Bravo AF: 0.719

Asia WGS AF: 0.541 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs6500610; hg19: chr16-4529613;