rs5995097

Variant names:

• chr22-35382968-A-C
• rs5995097
• NM_002133.3:c.24-138A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-35382968-A-C
• chr22-35382968-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002133.3(HMOX1):​c.24-138A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 1,234,270 control chromosomes in the GnomAD database, including 1,718 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.042 (164 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1554 hom.)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 4 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), Ambry Genetics, Orphanet, ClinGen
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 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.24-138A>C		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.24-138A>C		intron	N/A	ENSP00000216117.8	P09601
	HMOX1	ENST00000679074.1		c.24-138A>C		intron	N/A	ENSP00000503459.1	A0A7I2V3I1
	HMOX1	ENST00000412893.5	TSL:3	c.24-138A>C		intron	N/A	ENSP00000413316.1	B1AHA8

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6324 AN: 152208 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0505 AC: 54645 AN: 1081944 Hom.: 1554 AF XY: 0.0496 AC XY: 27309 AN XY: 550366

African (AFR) AF: 0.0235 AC: 603 AN: 25648

American (AMR) AF: 0.0433 AC: 1794 AN: 41414

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 471 AN: 21804

East Asian (EAS) AF: 0.0625 AC: 2120 AN: 33934

South Asian (SAS) AF: 0.0246 AC: 1915 AN: 77742

European-Finnish (FIN) AF: 0.0451 AC: 1695 AN: 37574

Middle Eastern (MID) AF: 0.0152 AC: 63 AN: 4144

European-Non Finnish (NFE) AF: 0.0552 AC: 43823 AN: 793438

Other (OTH) AF: 0.0467 AC: 2161 AN: 46246

GnomAD4 genome AF: 0.0416 AC: 6337 AN: 152326 Hom.: 164 Cov.: 32 AF XY: 0.0411 AC XY: 3064 AN XY: 74496

African (AFR) AF: 0.0252 AC: 1049 AN: 41578

American (AMR) AF: 0.0344 AC: 526 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.0547 AC: 283 AN: 5178

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4828

European-Finnish (FIN) AF: 0.0494 AC: 525 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0532 AC: 3618 AN: 68020

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0480 Hom.: 34

Bravo AF: 0.0406

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-0.46
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5995097;

hg19: chr22-35778961;