GeneBe

rs549270240

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000190.4(HMBS):​c.33+114_33+135delTTTTTTTTTTTTTTTTTTTTTT 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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

Publications

0 publications found
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]
HMBS Gene-Disease associations (from GenCC):
  • acute intermittent porphyria
    Inheritance: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High AC in GnomAd4 at 14 SD,AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMBSNM_000190.4 linkc.33+114_33+135delTTTTTTTTTTTTTTTTTTTTTT intron_variant Intron 1 of 13 ENST00000652429.1 NP_000181.2 P08397-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMBSENST00000652429.1 linkc.33+107_33+128delTTTTTTTTTTTTTTTTTTTTTT intron_variant Intron 1 of 13 NM_000190.4 ENSP00000498786.1 P08397-1

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
African (AFR)
AF:
0.000163
AC:
3
AN:
18384
American (AMR)
AF:
0.00
AC:
0
AN:
11818
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
10372
East Asian (EAS)
AF:
0.00
AC:
0
AN:
7824
South Asian (SAS)
AF:
0.00
AC:
0
AN:
50144
European-Finnish (FIN)
AF:
0.000176
AC:
2
AN:
11370
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1920
European-Non Finnish (NFE)
AF:
0.000170
AC:
101
AN:
593392
Other (OTH)
AF:
0.000217
AC:
6
AN:
27608
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.588
Heterozygous variant carriers
0
4
7
11
14
18
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
African (AFR)
AF:
0.000109
AC:
2
AN:
18368
American (AMR)
AF:
0.000209
AC:
1
AN:
4790
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2142
East Asian (EAS)
AF:
0.00
AC:
0
AN:
1402
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1312
European-Finnish (FIN)
AF:
0.000888
AC:
1
AN:
1126
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
80
European-Non Finnish (NFE)
AF:
0.000276
AC:
10
AN:
36236
Other (OTH)
AF:
0.00
AC:
0
AN:
852
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.771
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
67

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.8

Splicing

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

Publications

Other links and lift over

dbSNP: rs549270240; hg19: chr11-118955882; API