16-4485556-C-T

Variant names:

• chr16-4485556-C-T
• rs2160567
• NM_002134.4:c.-42+9069C>T

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+9069C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,748 control chromosomes in the GnomAD database, including 25,824 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 0.55 (25824 hom., cov: 30)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 19 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.-42+9069C>T		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+9069C>T		intron_variant	Intron 1 of 5	1	NM_002134.4	ENSP00000459214.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82882 AN: 151630 Hom.: 25814 Cov.: 30

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.546 AC: 82912 AN: 151748 Hom.: 25824 Cov.: 30 AF XY: 0.546 AC XY: 40478 AN XY: 74144

African (AFR) AF: 0.231 AC: 9559 AN: 41312

American (AMR) AF: 0.555 AC: 8438 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2170 AN: 3470

East Asian (EAS) AF: 0.643 AC: 3316 AN: 5158

South Asian (SAS) AF: 0.542 AC: 2609 AN: 4814

European-Finnish (FIN) AF: 0.731 AC: 7704 AN: 10544

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.697 AC: 47346 AN: 67930

Other (OTH) AF: 0.572 AC: 1205 AN: 2108

Alfa AF: 0.641 Hom.: 23823

Bravo AF: 0.522

Asia WGS AF: 0.497 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.57
PhyloP100		0.088
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: rs2160567; hg19: chr16-4535557;