chr11-119085086-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PP3_ModerateBP6_ModerateBS1BS2
The NM_000190.4(HMBS):c.33+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,610,820 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0025 ( 4 hom., cov: 31)
Exomes 𝑓: 0.00025 ( 1 hom. )
Consequence
HMBS
NM_000190.4 intron
NM_000190.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.455
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 11-119085086-C-G is Benign according to our data. Variant chr11-119085086-C-G is described in ClinVar as [Benign]. Clinvar id is 1657993.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00255 (386/151430) while in subpopulation AFR AF= 0.00885 (366/41364). AF 95% confidence interval is 0.0081. There are 4 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 4 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HMBS | NM_000190.4 | c.33+20C>G | intron_variant | ENST00000652429.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HMBS | ENST00000652429.1 | c.33+20C>G | intron_variant | NM_000190.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00256 AC: 387AN: 151324Hom.: 4 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
387
AN:
151324
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000678 AC: 169AN: 249086Hom.: 1 AF XY: 0.000495 AC XY: 67AN XY: 135328
GnomAD3 exomes
AF:
AC:
169
AN:
249086
Hom.:
AF XY:
AC XY:
67
AN XY:
135328
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000245 AC: 358AN: 1459390Hom.: 1 Cov.: 43 AF XY: 0.000215 AC XY: 156AN XY: 726018
GnomAD4 exome
AF:
AC:
358
AN:
1459390
Hom.:
Cov.:
43
AF XY:
AC XY:
156
AN XY:
726018
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00255 AC: 386AN: 151430Hom.: 4 Cov.: 31 AF XY: 0.00227 AC XY: 168AN XY: 73944
GnomAD4 genome
?
AF:
AC:
386
AN:
151430
Hom.:
Cov.:
31
AF XY:
AC XY:
168
AN XY:
73944
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at