22-35394292-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 72 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3	c.*694T>C		downstream_gene_variant		ENST00000216117.9	NP_002124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9	c.*694T>C		downstream_gene_variant		1	NM_002133.3	ENSP00000216117.8

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000450

Gnomad4 OTH exome AF: 0.00676

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

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.00381

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00905

Alfa AF: 0.0122 Hom.: 11

Bravo AF: 0.0158

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12160039; hg19: chr22-35790285;