22-35387624-G-A

Position:

• chr22-35387624-G-A

Variant summary

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

The NM_002133.3(HMOX1):​c.636+448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,226 control chromosomes in the GnomAD database, including 3,959 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 0.16 (3959 hom., cov: 33)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.636+448G>A		intron_variant		ENST00000216117.9	NP_002124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9	c.636+448G>A		intron_variant		1	NM_002133.3	ENSP00000216117.8

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23842 AN: 152108 Hom.: 3954 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.157 AC: 23889 AN: 152226 Hom.: 3959 Cov.: 33 AF XY: 0.151 AC XY: 11242 AN XY: 74434

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.0885

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0529

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0797 Hom.: 508

Bravo AF: 0.174

Asia WGS AF: 0.0950 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.4
DANN	Benign	0.84

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: rs11912889; hg19: chr22-35783617;