NM_002133.3:c.*694T>C

Variant names:

• chr22-35394292-T-C
• rs12160039
• NM_002133.3:c.*694T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002133.3(HMOX1):​c.*694T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 155,832 control chromosomes in the GnomAD database, including 72 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 0.014 (72 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (0 hom.)
• Consequence: HMOX1 NM_002133.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2144/151842) while in subpopulation AFR AF = 0.0494 (2043/41374). AF 95% confidence interval is 0.0476. There are 72 homozygotes in GnomAd4. There are 1021 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 72 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	NM_002133.3	MANE Select	c.*694T>C		downstream_gene	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.*694T>C		downstream_gene	N/A	ENSP00000216117.8
	HMOX1	ENST00000679074.1		c.*711T>C		downstream_gene	N/A	ENSP00000503459.1
	HMOX1	ENST00000678411.1		c.*694T>C		downstream_gene	N/A	ENSP00000503526.1

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2132 AN: 151724 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00388

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00914

GnomAD4 exome AF: 0.000752 AC: 3 AN: 3990 Hom.: 0 AF XY: 0.000483 AC XY: 1 AN XY: 2070

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AF: 0.00114 AC: 1 AN: 880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 110

South Asian (SAS) AF: 0.00 AC: 0 AN: 344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.000450 AC: 1 AN: 2224

Other (OTH) AF: 0.00676 AC: 1 AN: 148

GnomAD4 genome AF: 0.0141 AC: 2144 AN: 151842 Hom.: 72 Cov.: 32 AF XY: 0.0138 AC XY: 1021 AN XY: 74214

African (AFR) AF: 0.0494 AC: 2043 AN: 41374

American (AMR) AF: 0.00381 AC: 58 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67960

Other (OTH) AF: 0.00905 AC: 19 AN: 2100

Alfa AF: 0.0134 Hom.: 11

Bravo AF: 0.0158

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.45
DANN	Benign	0.37
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs12160039; hg19: chr22-35790285;