16-4490226-A-G

Position:

• chr16-4490226-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+13739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,226 control chromosomes in the GnomAD database, including 2,032 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 0.11 (2032 hom., cov: 32)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.-42+13739A>G		intron_variant		ENST00000570646.6	NP_002125.3
LOC124903636	XR_007064964.1	n.409+5056T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX2	ENST00000570646.6	c.-42+13739A>G		intron_variant		1	NM_002134.4	ENSP00000459214	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17203 AN: 152108 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0946

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17221 AN: 152226 Hom.: 2032 Cov.: 32 AF XY: 0.110 AC XY: 8215 AN XY: 74438

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.0601 Hom.: 299

Bravo AF: 0.129

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.87

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: rs8055559; hg19: chr16-4540227;