22-35381208-G-GCGCGGGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002133.3(HMOX1):c.23+22_23+28dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 1,546,396 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (43 hom.)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.145

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 -10 ACMG points.

• BP6: Variant 22-35381208-G-GCGCGGGA is Benign according to our data. Variant chr22-35381208-G-GCGCGGGA is described in ClinVar as [Benign]. Clinvar id is 1168720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00444 (677/152364) while in subpopulation NFE AF= 0.00653 (444/68036). AF 95% confidence interval is 0.00602. There are 3 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX1	NM_002133.3	c.23+22_23+28dup		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.23+22_23+28dup		intron_variant		1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.00445 AC: 678 AN: 152246 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00653

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00462 AC: 661 AN: 143132 Hom.: 2 AF XY: 0.00455 AC XY: 358 AN XY: 78606

Gnomad AFR exome AF: 0.00189

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.0160

Gnomad EAS exome AF: 0.00771

Gnomad SAS exome AF: 0.000346

Gnomad FIN exome AF: 0.000292

Gnomad NFE exome AF: 0.00602

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00619 AC: 8635 AN: 1394032 Hom.: 43 Cov.: 31 AF XY: 0.00601 AC XY: 4142 AN XY: 688930

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00276

Gnomad4 ASJ exome AF: 0.0161

Gnomad4 EAS exome AF: 0.00660

Gnomad4 SAS exome AF: 0.000388

Gnomad4 FIN exome AF: 0.000729

Gnomad4 NFE exome AF: 0.00682

Gnomad4 OTH exome AF: 0.00644

GnomAD4 genome AF: 0.00444 AC: 677 AN: 152364 Hom.: 3 Cov.: 32 AF XY: 0.00411 AC XY: 306 AN XY: 74518

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00653

Gnomad4 OTH AF: 0.00426

Bravo AF: 0.00482

Asia WGS AF: 0.00144 AC: 5 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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs552022839; hg19: chr22-35777201;