NM_002133.3:c.144+349G>A

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_002133.3(HMOX1):c.144+349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.154 (AC=23,357) in the gnomAD database across 152,146 control chromosomes, including 3,755 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.407. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 3755 hom., cov: 31)

Consequence

HMOX1
NM_002133.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.612

Publications

3 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: Orphanet, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
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:

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new If you want to explore the variant's impact on the transcript NM_002133.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4067 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002133.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMOX1	NM_002133.3	MANE Select	c.144+349G>A		intron	N/A	NP_002124.1	P09601

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMOX1	ENST00000216117.9	TSL:1 MANE Select	c.144+349G>A	intron	N/A	ENSP00000216117.8	P09601
HMOX1	ENST00000679074.1		c.144+349G>A	intron	N/A	ENSP00000503459.1	A0A7I2V3I1
HMOX1	ENST00000412893.5	TSL:3	c.144+349G>A	intron	N/A	ENSP00000413316.1	B1AHA8

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	0.153	23311	3751	152028	31
GnomAD4 genome	0.154	23357	3755	152146	31
TOPMed (Bravo)	0.170
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.118	5869	839	49538
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	0.133	312	37	2342
ChinaMAP Phase 1	0.0508
Denmark Genome	0.0567	17		300
GenomeAsia100K	0.0940	331		3478
Korea4K (4,157 Koreans)	0.0480	347		7234
Qatari Genome	0.159	28		176
ToMMo 61KJPN (+60KJPN MNV)	0.0471	5777	133	122692
Turkish Variome	0.0776	120	4	1546
UK10K	0.0558	422		7562

Showing 13 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Uncertain	-	14
BayesDel_noAF	Benign	-	-0.86
CADD	Benign	-	13
DANN	Benign	-	0.78
GPN-Star LLR	N/A	-	0.27
GPN-Star score	N/A	-	-0.27
Mutation Taster	N/A	polymorphism (auto)	100/0
PhyloP100	Benign	-	0.61
PromoterAI	N/A	Neutral	-0.036

Showing 9 of 9 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

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