22-35382007-C-A

Position:

• chr22-35382007-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002133.3(HMOX1):​c.23+811C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 152,274 control chromosomes in the GnomAD database, including 118 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 0.037 (118 hom., cov: 32)
• Consequence: HMOX1 NM_002133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0373 (5677/152274) while in subpopulation NFE AF= 0.0505 (3433/68016). AF 95% confidence interval is 0.0491. There are 118 homozygotes in gnomad4. There are 2538 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 118 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMOX1	NM_002133.3	c.23+811C>A		intron_variant		ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.23+811C>A		intron_variant		1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5677 AN: 152156 Hom.: 119 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0447

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0373 AC: 5677 AN: 152274 Hom.: 118 Cov.: 32 AF XY: 0.0341 AC XY: 2538 AN XY: 74464

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0134

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0386 Hom.: 19

Bravo AF: 0.0405

Asia WGS AF: 0.0180 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs17883018; hg19: chr22-35778000;