22-35381192-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D7E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.042 (161 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2058 hom.)
• Consequence: HMOX1 NM_002133.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.311

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 -14 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_single_submitter, 1 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	UniProt
HMOX1	NM_002133.3	c.19G>C	p.Asp7His	missense_variant	1/5	ENST00000216117.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMOX1	ENST00000216117.9	c.19G>C	p.Asp7His	missense_variant	1/5	1	NM_002133.3	P1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6317 AN: 152214 Hom.: 161 Cov.: 32

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

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.: 31 AF XY: 0.0513 AC XY: 35375 AN XY: 689346

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.: 32 AF XY: 0.0411 AC XY: 3059 AN XY: 74490

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.: 26

Bravo AF: 0.0404

TwinsUK AF: 0.0539 AC: 200

ALSPAC AF: 0.0555 AC: 214

ESP6500AA AF: 0.0162 AC: 60

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	16
Dann	Benign	0.91
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.72	T;T
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.88	N
PrimateAI	Uncertain	0.54	T
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	T
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

Other links and lift over

dbSNP: rs2071747; hg19: chr22-35777185; COSMIC: COSV53340374; COSMIC: COSV53340374;