chr22-35386666-C-T

Variant names:

• chr22-35386666-C-T
• rs17879606
• NM_002133.3:c.145-19C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0500
• Publications: 5 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
• 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 -20 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 VariationId is 1166902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	NM_002133.3	MANE Select	c.145-19C>T		intron	N/A	NP_002124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	ENST00000216117.9	TSL:1 MANE Select	c.145-19C>T		intron	N/A	ENSP00000216117.8
	HMOX1	ENST00000679074.1		c.145-19C>T		intron	N/A	ENSP00000503459.1
	HMOX1	ENST00000412893.5	TSL:3	c.145-19C>T		intron	N/A	ENSP00000413316.1

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

GnomAD2 exomes AF: 0.0355 AC: 8865 AN: 249514 AF XY: 0.0360

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 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

African (AFR) AF: 0.0248 AC: 830 AN: 33476

American (AMR) AF: 0.0347 AC: 1552 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 1110 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39692

South Asian (SAS) AF: 0.0161 AC: 1388 AN: 86226

European-Finnish (FIN) AF: 0.0176 AC: 940 AN: 53396

Middle Eastern (MID) AF: 0.0702 AC: 405 AN: 5766

European-Non Finnish (NFE) AF: 0.0508 AC: 56535 AN: 1111822

Other (OTH) AF: 0.0466 AC: 2816 AN: 60380

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

African (AFR) AF: 0.0238 AC: 988 AN: 41574

American (AMR) AF: 0.0445 AC: 681 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 138 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4826

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10620

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3436 AN: 68020

Other (OTH) AF: 0.0527 AC: 111 AN: 2108

Alfa AF: 0.0448 Hom.: 59

Bravo AF: 0.0405

Asia WGS AF: 0.0180 AC: 66 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.8
DANN	Benign	0.84
PhyloP100		-0.050
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17879606; hg19: chr22-35782659;