rs4785969

Positions:

• chr16-4486933-T-A
• chr16-4486933-T-C
• chr16-4486933-T-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+10446T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,092 control chromosomes in the GnomAD database, including 41,077 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 (41077 hom., cov: 32)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.-42+10446T>A		intron_variant		ENST00000570646.6	NP_002125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX2	ENST00000570646.6	c.-42+10446T>A		intron_variant		1	NM_002134.4	ENSP00000459214.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111362 AN: 151974 Hom.: 41024 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.733 AC: 111470 AN: 152092 Hom.: 41077 Cov.: 32 AF XY: 0.728 AC XY: 54093 AN XY: 74320

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.719

Alfa AF: 0.673 Hom.: 2030

Bravo AF: 0.734

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
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: rs4785969; hg19: chr16-4536934;