chr16-4485556-C-T

Position:

• chr16-4485556-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.-42+9069C>T		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+9069C>T		intron_variant		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

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.572

Alfa AF: 0.650 Hom.: 17050

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

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: rs2160567; hg19: chr16-4535557;