Variant 22-35381192-G-C 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.19G>C(p.Asp7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,547,162 control chromosomes in the GnomAD database, including 2,219 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.042 ( 161 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2058 hom. )

Consequence

HMOX1
NM_002133.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.311

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 (MetaRNN=0.002096802).

BP6

Variant 22-35381192-G-C is Benign according to our data. Variant chr22-35381192-G-C is described in ClinVar as [Benign]. Clinvar id is 1168542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0527 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.19G>C	p.Asp7His	missense_variant	1/5	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.19G>C	p.Asp7His	missense_variant	1/5	1	NM_002133.3	ENSP00000216117.8		P09601

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6317

AN:

152214

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0340

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.0586

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0494

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0534

Gnomad OTH

AF:

0.0420

GnomAD3 exomes

AF:

0.0429

AC:

6202

AN:

144592

Hom.:

184

AF XY:

0.0419

AC XY:

3328

AN XY:

79362

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.0422

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.0529

Gnomad SAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.0492

Gnomad NFE exome

AF:

0.0543

Gnomad OTH exome

AF:

0.0407

GnomAD4 exome

AF:

0.0519

AC:

72432

AN:

1394830

Hom.:

2058

Cov.:

AF XY:

0.0513

AC XY:

35375

AN XY:

689346

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.0421

Gnomad4 ASJ exome

AF:

0.0225

Gnomad4 EAS exome

AF:

0.0721

Gnomad4 SAS exome

AF:

0.0245

Gnomad4 FIN exome

AF:

0.0470

Gnomad4 NFE exome

AF:

0.0559

Gnomad4 OTH exome

AF:

0.0461

GnomAD4 genome

AF:

0.0415

AC:

6326

AN:

152332

Hom.:

161

Cov.:

AF XY:

0.0411

AC XY:

3059

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.0581

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.0494

Gnomad4 NFE

AF:

0.0534

Gnomad4 OTH

AF:

0.0411

Alfa

AF:

0.0336

Hom.:

Bravo

AF:

0.0404

TwinsUK

AF:

0.0539

AC:

200

ALSPAC

AF:

0.0555

AC:

214

ESP6500AA

AF:

0.0162

AC:

ESP6500EA

AF:

0.0367

AC:

276

ExAC

AF:

0.0314

AC:

3393

Asia WGS

AF:

0.0370

AC:

128

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.21

.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

.;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.0010

.;B

Vest4

0.059

MPC

0.061

ClinPred

0.0028

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.28

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