rs17879606

chr22-35386666-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002133.3(HMOX1):c.145-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,613,852 control chromosomes in the GnomAD database, including 1,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (116 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1618 hom.)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 22-35386666-C-T is Benign according to our data. Variant chr22-35386666-C-T is described in ClinVar as [Benign]. Clinvar id is 1166902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX1	NM_002133.3	c.145-19C>T		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.145-19C>T		intron_variant		1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5675 AN: 152174 Hom.: 117 Cov.: 33

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0532

GnomAD3 exomes AF: 0.0355 AC: 8865 AN: 249514 Hom.: 180 AF XY: 0.0360 AC XY: 4856 AN XY: 134992

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.0331

Gnomad ASJ exome AF: 0.0455

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.0153

Gnomad FIN exome AF: 0.0163

Gnomad NFE exome AF: 0.0513

Gnomad OTH exome AF: 0.0472

GnomAD4 exome AF: 0.0449 AC: 65580 AN: 1461560 Hom.: 1618 Cov.: 34 AF XY: 0.0446 AC XY: 32449 AN XY: 727078

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.0347

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.0176

Gnomad4 NFE exome AF: 0.0508

Gnomad4 OTH exome AF: 0.0466

GnomAD4 genome AF: 0.0373 AC: 5675 AN: 152292 Hom.: 116 Cov.: 33 AF XY: 0.0341 AC XY: 2537 AN XY: 74466

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.0445

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0415 Hom.: 31

Bravo AF: 0.0405

Asia WGS AF: 0.0180 AC: 66 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	6.8
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: rs17879606; hg19: chr22-35782659;