GeneBe

rs549270240

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000190.4(HMBS):​c.33+114_33+135del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 799,600 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

HMBS
NM_000190.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83
Variant links:
Genes affected
HMBS (HGNC:4982): (hydroxymethylbilane synthase) This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HMBSNM_000190.4 linkuse as main transcriptc.33+114_33+135del intron_variant ENST00000652429.1 NP_000181.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HMBSENST00000652429.1 linkuse as main transcriptc.33+114_33+135del intron_variant NM_000190.4 ENSP00000498786 P3P08397-1

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
14
AN:
66768
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000109
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000209
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000888
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000276
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000153
AC:
112
AN:
732832
Hom.:
1
AF XY:
0.000124
AC XY:
45
AN XY:
362476
show subpopulations
Gnomad4 AFR exome
AF:
0.000163
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000176
Gnomad4 NFE exome
AF:
0.000170
Gnomad4 OTH exome
AF:
0.000217
GnomAD4 genome
AF:
0.000210
AC:
14
AN:
66768
Hom.:
0
Cov.:
0
AF XY:
0.000305
AC XY:
9
AN XY:
29496
show subpopulations
Gnomad4 AFR
AF:
0.000109
Gnomad4 AMR
AF:
0.000209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000888
Gnomad4 NFE
AF:
0.000276
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs549270240; hg19: chr11-118955882; API