rs9622194

Positions:

• chr22-35390970-G-A
• chr22-35390970-G-C

Variant summary

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

The ENST00000216117.9(HMOX1):​c.736+1007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,188 control chromosomes in the GnomAD database, including 3,429 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 0.12 (3429 hom., cov: 31)
• Consequence: HMOX1 ENST00000216117.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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 = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.736+1007G>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.736+1007G>A		intron_variant		1	NM_002133.3	ENSP00000216117	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18116 AN: 152070 Hom.: 3421 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00238

Gnomad OTH AF: 0.0788

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

GnomAD4 genome AF: 0.119 AC: 18168 AN: 152188 Hom.: 3429 Cov.: 31 AF XY: 0.117 AC XY: 8696 AN XY: 74404

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.0406

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00238

Gnomad4 OTH AF: 0.0784

Alfa AF: 0.00578 Hom.: 15

Bravo AF: 0.134

Asia WGS AF: 0.0770 AC: 267 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	4.3
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9622194; hg19: chr22-35786963;