Genetic Variant NM_002133.3:c.736+270T>C (chr22-35390233-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002133.3(HMOX1):c.736+270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 461,170 control chromosomes in the GnomAD database, including 25,413 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 0.28 ( 6480 hom., cov: 31)

Exomes 𝑓: 0.35 ( 18933 hom. )

Consequence

HMOX1
NM_002133.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.68

Publications

4 publications found

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 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)

HMOX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMOX1	NM_002133.3 link	c.736+270T>C		intron_variant	Intron 4 of 4	ENST00000216117.9	NP_002124.1	P09601Q6FH11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMOX1	ENST00000216117.9 link	c.736+270T>C		intron_variant	Intron 4 of 4	1	NM_002133.3	ENSP00000216117.8		P09601

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42891

AN:

151772

Hom.:

6489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.290

GnomAD4 exome

AF:

0.352

AC:

108872

AN:

309280

Hom.:

18933

Cov.:

AF XY:

0.358

AC XY:

59236

AN XY:

165412

show subpopulations

African (AFR)

AF:

0.195

AC:

1696

AN:

8686

American (AMR)

AF:

0.208

AC:

2946

AN:

14134

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

3392

AN:

9100

East Asian (EAS)

AF:

0.455

AC:

8833

AN:

19410

South Asian (SAS)

AF:

0.419

AC:

18255

AN:

43590

European-Finnish (FIN)

AF:

0.381

AC:

6190

AN:

16244

Middle Eastern (MID)

AF:

0.363

AC:

450

AN:

1238

European-Non Finnish (NFE)

AF:

0.341

AC:

61299

AN:

179974

Other (OTH)

AF:

0.344

AC:

5811

AN:

16904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3753

7506

11260

15013

18766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.282

AC:

42888

AN:

151890

Hom.:

6480

Cov.:

AF XY:

0.288

AC XY:

21350

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.183

AC:

7597

AN:

41426

American (AMR)

AF:

0.218

AC:

3329

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1195

AN:

3468

East Asian (EAS)

AF:

0.457

AC:

2353

AN:

5154

South Asian (SAS)

AF:

0.411

AC:

1984

AN:

4824

European-Finnish (FIN)

AF:

0.364

AC:

3834

AN:

10536

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.320

AC:

21711

AN:

67914

Other (OTH)

AF:

0.291

AC:

614

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1579

3158

4737

6316

7895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.285

Hom.:

796

Bravo

AF:

0.265

Asia WGS

AF:

0.429

AC:

1493

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.46

(source)

DANN

Benign

0.084

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_002133.3:c.736+270T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over