chr16-4475264-C-T

Variant names:

• chr16-4475264-C-T
• rs4786500
• NM_001127206.3:c.-42+417C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127206.3(HMOX2):​c.-42+417C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,766 control chromosomes in the GnomAD database, including 38,153 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 0.71 (38153 hom., cov: 30)
• Consequence: HMOX2 NM_001127206.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 26 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127206.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	NM_001127206.3		c.-42+417C>T		intron	N/A	NP_001120678.1	P30519-1
	NMRAL1	NM_001351994.2		c.-273-472G>A		intron	N/A	NP_001338923.1	Q9HBL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX2	ENST00000406590.6	TSL:5	c.-42+417C>T		intron	N/A	ENSP00000385100.2	P30519-1
	HMOX2	ENST00000905894.1		c.-42+547C>T		intron	N/A	ENSP00000575953.1
	HMOX2	ENST00000938913.1		c.-42+558C>T		intron	N/A	ENSP00000608972.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107335 AN: 151644 Hom.: 38106 Cov.: 30

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.587

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.708 AC: 107433 AN: 151766 Hom.: 38153 Cov.: 30 AF XY: 0.704 AC XY: 52180 AN XY: 74144

African (AFR) AF: 0.708 AC: 29298 AN: 41370

American (AMR) AF: 0.697 AC: 10624 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2360 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3275 AN: 5108

South Asian (SAS) AF: 0.553 AC: 2658 AN: 4808

European-Finnish (FIN) AF: 0.749 AC: 7920 AN: 10568

Middle Eastern (MID) AF: 0.587 AC: 169 AN: 288

European-Non Finnish (NFE) AF: 0.725 AC: 49237 AN: 67910

Other (OTH) AF: 0.701 AC: 1473 AN: 2102

Alfa AF: 0.715 Hom.: 55862

Bravo AF: 0.707

Asia WGS AF: 0.538 AC: 1870 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.58
PhyloP100		0.021
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: rs4786500; hg19: chr16-4525265;