rs2285112

chr22-35393270-A-Gchr22-35393270-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002133.3(HMOX1):c.737-198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,990 control chromosomes in the GnomAD database, including 17,810 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 0.46 (17810 hom., cov: 32)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

Genes affected

HMOX1 (HGNC:5013): (heme oxygenase 1) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX1	NM_002133.3	c.737-198A>G		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.737-198A>G		intron_variant		1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70560 AN: 151874 Hom.: 17789 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.465 AC: 70623 AN: 151990 Hom.: 17810 Cov.: 32 AF XY: 0.463 AC XY: 34408 AN XY: 74298

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.448

Alfa AF: 0.397 Hom.: 13504

Bravo AF: 0.467

Asia WGS AF: 0.537 AC: 1872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.9
Dann	Benign	0.81

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: rs2285112; hg19: chr22-35789263; COSMIC: COSV53340942; COSMIC: COSV53340942;