rs2071748

chr22-35381625-G-Achr22-35381625-G-T

Variant summary

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

The NM_002133.3(HMOX1):c.23+429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,844 control chromosomes in the GnomAD database, including 15,966 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 0.44 (15966 hom., cov: 30)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.12

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX1	NM_002133.3	c.23+429G>A		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.23+429G>A		intron_variant		1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67224 AN: 151726 Hom.: 15954 Cov.: 30

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.443 AC: 67277 AN: 151844 Hom.: 15966 Cov.: 30 AF XY: 0.442 AC XY: 32815 AN XY: 74164

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.422

Alfa AF: 0.375 Hom.: 17813

Bravo AF: 0.444

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.36
Dann	Benign	0.59

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: rs2071748; hg19: chr22-35777618;