16-4499225-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002134.4(HMOX2):​c.-41-6259C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,148 control chromosomes in the GnomAD database, including 33,719 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 0.66 ( 33719 hom., cov: 33)

Consequence

HMOX2
NM_002134.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206
Variant links:
Genes affected
HMOX2 (HGNC:5014): (heme oxygenase 2) 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. Several alternatively spliced transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HMOX2NM_002134.4 linkuse as main transcriptc.-41-6259C>G intron_variant ENST00000570646.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMOX2ENST00000570646.6 linkuse as main transcriptc.-41-6259C>G intron_variant 1 NM_002134.4 P1P30519-1

Frequencies

GnomAD3 genomes
AF:
0.658
AC:
100070
AN:
152026
Hom.:
33709
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.520
Gnomad AMI
AF:
0.461
Gnomad AMR
AF:
0.680
Gnomad ASJ
AF:
0.669
Gnomad EAS
AF:
0.646
Gnomad SAS
AF:
0.559
Gnomad FIN
AF:
0.758
Gnomad MID
AF:
0.570
Gnomad NFE
AF:
0.733
Gnomad OTH
AF:
0.667
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.658
AC:
100114
AN:
152148
Hom.:
33719
Cov.:
33
AF XY:
0.655
AC XY:
48710
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.519
Gnomad4 AMR
AF:
0.680
Gnomad4 ASJ
AF:
0.669
Gnomad4 EAS
AF:
0.645
Gnomad4 SAS
AF:
0.560
Gnomad4 FIN
AF:
0.758
Gnomad4 NFE
AF:
0.733
Gnomad4 OTH
AF:
0.661
Alfa
AF:
0.702
Hom.:
4769
Bravo
AF:
0.649
Asia WGS
AF:
0.529
AC:
1839
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.6
DANN
Benign
0.41

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.

Other links and lift over

dbSNP: rs1362626; hg19: chr16-4549226; API