Variant chr22-35386666-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002133.3(HMOX1):c.145-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,613,852 control chromosomes in the GnomAD database, including 1,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 116 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1618 hom. )

Consequence

HMOX1
NM_002133.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0500

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 22-35386666-C-T is Benign according to our data. Variant chr22-35386666-C-T is described in ClinVar as [Benign]. Clinvar id is 1166902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMOX1	NM_002133.3 linkuse as main transcript	c.145-19C>T		intron_variant		ENST00000216117.9	NP_002124.1	P09601Q6FH11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9 linkuse as main transcript	c.145-19C>T		intron_variant		1	NM_002133.3	ENSP00000216117.8		P09601

Frequencies

GnomAD3 genomes

AF:

0.0373

AC:

5675

AN:

152174

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0446

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0133

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0505

Gnomad OTH

AF:

0.0532

GnomAD3 exomes

AF:

0.0355

AC:

8865

AN:

249514

Hom.:

180

AF XY:

0.0360

AC XY:

4856

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.0243

Gnomad AMR exome

AF:

0.0331

Gnomad ASJ exome

AF:

0.0455

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0513

Gnomad OTH exome

AF:

0.0472

GnomAD4 exome

AF:

0.0449

AC:

65580

AN:

1461560

Hom.:

1618

Cov.:

AF XY:

0.0446

AC XY:

32449

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0248

Gnomad4 AMR exome

AF:

0.0347

Gnomad4 ASJ exome

AF:

0.0425

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0161

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.0508

Gnomad4 OTH exome

AF:

0.0466

GnomAD4 genome

AF:

0.0373

AC:

5675

AN:

152292

Hom.:

116

Cov.:

AF XY:

0.0341

AC XY:

2537

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0238

Gnomad4 AMR

AF:

0.0445

Gnomad4 ASJ

AF:

0.0397

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0124

Gnomad4 FIN

AF:

0.0133

Gnomad4 NFE

AF:

0.0505

Gnomad4 OTH

AF:

0.0527

Alfa

AF:

0.0415

Hom.:

Bravo

AF:

0.0405

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.8

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over