chr16-4487692-T-C

Variant names:

• chr16-4487692-T-C
• rs4786504
• NM_002134.4:c.-42+11205T>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.-42+11205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,024 control chromosomes in the GnomAD database, including 40,904 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 0.73 (40904 hom., cov: 29)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 12 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.-42+11205T>C		intron_variant	Intron 1 of 5	ENST00000570646.6	NP_002125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX2	ENST00000570646.6	c.-42+11205T>C		intron_variant	Intron 1 of 5	1	NM_002134.4	ENSP00000459214.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 110806 AN: 150902 Hom.: 40849 Cov.: 29

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.734 AC: 110917 AN: 151024 Hom.: 40904 Cov.: 29 AF XY: 0.729 AC XY: 53742 AN XY: 73714

African (AFR) AF: 0.783 AC: 32152 AN: 41076

American (AMR) AF: 0.707 AC: 10750 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2377 AN: 3466

East Asian (EAS) AF: 0.641 AC: 3265 AN: 5090

South Asian (SAS) AF: 0.560 AC: 2692 AN: 4806

European-Finnish (FIN) AF: 0.756 AC: 7866 AN: 10402

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.735 AC: 49721 AN: 67686

Other (OTH) AF: 0.722 AC: 1513 AN: 2096

Alfa AF: 0.691 Hom.: 2371

Bravo AF: 0.736

Asia WGS AF: 0.546 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.14
PhyloP100		-2.1
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: rs4786504; hg19: chr16-4537693;