rs8140669

chr22-35383851-T-A

Variant summary

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

The NM_002133.3(HMOX1):c.144+625T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 152,154 control chromosomes in the GnomAD database, including 2,146 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 0.096 (2146 hom., cov: 31)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX1	NM_002133.3	c.144+625T>A		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.144+625T>A		intron_variant		1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14517 AN: 152036 Hom.: 2142 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.0619

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

GnomAD4 genome AF: 0.0956 AC: 14549 AN: 152154 Hom.: 2146 Cov.: 31 AF XY: 0.0937 AC XY: 6974 AN XY: 74410

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00218

Gnomad4 OTH AF: 0.0617

Alfa AF: 0.0723 Hom.: 164

Bravo AF: 0.106

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	15
Dann	Benign	0.83

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: rs8140669; hg19: chr22-35779844;