NM_002133.3:c.23+22_23+28dupCGGGACG

Variant names:

• chr22-35381208-G-GCGCGGGA
• rs552022839
• NM_002133.3:c.23+22_23+28dupCGGGACG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002133.3(HMOX1):​c.23+22_23+28dupCGGGACG 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
• Publications: 1 publications found

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]

HMOX1 Gene-Disease associations (from GenCC):

• heme oxygenase 1 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• chronic obstructive pulmonary disease

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002133.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	NM_002133.3	MANE Select	c.23+22_23+28dupCGGGACG		intron	N/A	NP_002124.1	Q6FH11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	ENST00000216117.9	TSL:1 MANE Select	c.23+22_23+28dupCGGGACG		intron	N/A	ENSP00000216117.8	P09601
	HMOX1	ENST00000679074.1		c.23+22_23+28dupCGGGACG		intron	N/A	ENSP00000503459.1	A0A7I2V3I1
	HMOX1	ENST00000412893.5	TSL:3	c.23+22_23+28dupCGGGACG		intron	N/A	ENSP00000413316.1	B1AHA8

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

GnomAD2 exomes AF: 0.00462 AC: 661 AN: 143132 AF XY: 0.00455

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 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

African (AFR) AF: 0.00140 AC: 45 AN: 32190

American (AMR) AF: 0.00276 AC: 101 AN: 36594

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 405 AN: 25216

East Asian (EAS) AF: 0.00660 AC: 241 AN: 36524

South Asian (SAS) AF: 0.000388 AC: 31 AN: 79920

European-Finnish (FIN) AF: 0.000729 AC: 26 AN: 35658

Middle Eastern (MID) AF: 0.00246 AC: 14 AN: 5694

European-Non Finnish (NFE) AF: 0.00682 AC: 7397 AN: 1084010

Other (OTH) AF: 0.00644 AC: 375 AN: 58226

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

African (AFR) AF: 0.00207 AC: 86 AN: 41590

American (AMR) AF: 0.00307 AC: 47 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00653 AC: 444 AN: 68036

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00468 Hom.: 0

Bravo AF: 0.00482

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs552022839; hg19: chr22-35777201;