rs9936357

Positions:

• chr16-4496985-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002134.4(HMOX2):​c.-41-8499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 152,056 control chromosomes in the GnomAD database, including 48 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 0.015 (48 hom., cov: 31)
• Consequence: HMOX2 NM_002134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2210/152056) while in subpopulation AFR AF= 0.0511 (2118/41440). AF 95% confidence interval is 0.0493. There are 48 homozygotes in gnomad4. There are 1052 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX2	NM_002134.4	c.-41-8499C>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.-41-8499C>T		intron_variant		1	NM_002134.4	ENSP00000459214.1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2203 AN: 151938 Hom.: 48 Cov.: 31

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00813

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

GnomAD4 genome AF: 0.0145 AC: 2210 AN: 152056 Hom.: 48 Cov.: 31 AF XY: 0.0142 AC XY: 1052 AN XY: 74346

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.00452

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.0143 Hom.: 5

Bravo AF: 0.0165

Asia WGS AF: 0.00231 AC: 8 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	2.1
DANN	Benign	0.32

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: rs9936357; hg19: chr16-4546986;