rs17885925

Variant names:

• chr22-35383230-T-C
• rs17885925
• NM_002133.3:c.144+4T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-35383230-T-C
• chr22-35383230-T-A

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.144+4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,612,922 control chromosomes in the GnomAD database, including 1,739 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (116 hom., cov: 31)
  • Exomes 𝑓: 0.045 (1623 hom.)
• Consequence: HMOX1 NM_002133.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002314
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.758
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 22-35383230-T-C is Benign according to our data. Variant chr22-35383230-T-C is described in ClinVar as Benign. ClinVar VariationId is 1167966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.065 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	NM_002133.3	MANE Select	c.144+4T>C		splice_region 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.144+4T>C		splice_region intron	N/A	ENSP00000216117.8	P09601
	HMOX1	ENST00000679074.1		c.144+4T>C		splice_region intron	N/A	ENSP00000503459.1	A0A7I2V3I1
	HMOX1	ENST00000412893.5	TSL:3	c.144+4T>C		splice_region intron	N/A	ENSP00000413316.1	B1AHA8

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5687 AN: 152162 Hom.: 117 Cov.: 31

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0506

Gnomad OTH AF: 0.0522

GnomAD2 exomes AF: 0.0358 AC: 9000 AN: 251236 AF XY: 0.0363

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.0336

Gnomad ASJ exome AF: 0.0456

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0165

Gnomad NFE exome AF: 0.0517

Gnomad OTH exome AF: 0.0473

GnomAD4 exome AF: 0.0449 AC: 65623 AN: 1460642 Hom.: 1623 Cov.: 32 AF XY: 0.0447 AC XY: 32462 AN XY: 726624

African (AFR) AF: 0.0248 AC: 830 AN: 33460

American (AMR) AF: 0.0351 AC: 1570 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 1108 AN: 26088

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39652

South Asian (SAS) AF: 0.0161 AC: 1387 AN: 86218

European-Finnish (FIN) AF: 0.0176 AC: 937 AN: 53302

Middle Eastern (MID) AF: 0.0706 AC: 407 AN: 5762

European-Non Finnish (NFE) AF: 0.0509 AC: 56567 AN: 1111166

Other (OTH) AF: 0.0466 AC: 2813 AN: 60320

GnomAD4 genome AF: 0.0373 AC: 5687 AN: 152280 Hom.: 116 Cov.: 31 AF XY: 0.0342 AC XY: 2546 AN XY: 74464

African (AFR) AF: 0.0238 AC: 988 AN: 41554

American (AMR) AF: 0.0451 AC: 690 AN: 15294

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4822

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0506 AC: 3439 AN: 68014

Other (OTH) AF: 0.0516 AC: 109 AN: 2112

Alfa AF: 0.0383 Hom.: 90

Bravo AF: 0.0405

Asia WGS AF: 0.0180 AC: 66 AN: 3478

EpiCase AF: 0.0586

EpiControl AF: 0.0570

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		-0.76
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.028
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: rs17885925; hg19: chr22-35779223;