rs1805312

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000409155.8(ALAD):​c.398-34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 1,607,220 control chromosomes in the GnomAD database, including 7,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 810 hom., cov: 33)
Exomes 𝑓: 0.086 ( 7139 hom. )

Consequence

ALAD
ENST00000409155.8 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.27
Variant links:
Genes affected
ALAD (HGNC:395): (aminolevulinate dehydratase) The ALAD enzyme is composed of 8 identical subunits and catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is essential for enzymatic activity. ALAD enzymatic activity is inhibited by lead and a defect in the ALAD structural gene can cause increased sensitivity to lead poisoning and acute hepatic porphyria. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 9-113390710-C-G is Benign according to our data. Variant chr9-113390710-C-G is described in ClinVar as [Benign]. Clinvar id is 1178261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALADNM_000031.6 linkuse as main transcriptc.398-34G>C intron_variant ENST00000409155.8 NP_000022.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALADENST00000409155.8 linkuse as main transcriptc.398-34G>C intron_variant 1 NM_000031.6 ENSP00000386284 P1P13716-1
ALADENST00000464749.5 linkuse as main transcriptn.481G>C non_coding_transcript_exon_variant 3/34
ALADENST00000468504.5 linkuse as main transcriptn.607G>C non_coding_transcript_exon_variant 5/75
ALADENST00000482847.5 linkuse as main transcriptn.671-34G>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0786
AC:
11965
AN:
152140
Hom.:
801
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0199
Gnomad AMI
AF:
0.0626
Gnomad AMR
AF:
0.210
Gnomad ASJ
AF:
0.0559
Gnomad EAS
AF:
0.151
Gnomad SAS
AF:
0.0677
Gnomad FIN
AF:
0.0766
Gnomad MID
AF:
0.0348
Gnomad NFE
AF:
0.0818
Gnomad OTH
AF:
0.0923
GnomAD3 exomes
AF:
0.114
AC:
26537
AN:
233556
Hom.:
2680
AF XY:
0.105
AC XY:
13317
AN XY:
126626
show subpopulations
Gnomad AFR exome
AF:
0.0172
Gnomad AMR exome
AF:
0.328
Gnomad ASJ exome
AF:
0.0537
Gnomad EAS exome
AF:
0.152
Gnomad SAS exome
AF:
0.0712
Gnomad FIN exome
AF:
0.0775
Gnomad NFE exome
AF:
0.0797
Gnomad OTH exome
AF:
0.0954
GnomAD4 exome
AF:
0.0856
AC:
124614
AN:
1454962
Hom.:
7139
Cov.:
35
AF XY:
0.0848
AC XY:
61355
AN XY:
723378
show subpopulations
Gnomad4 AFR exome
AF:
0.0136
Gnomad4 AMR exome
AF:
0.317
Gnomad4 ASJ exome
AF:
0.0547
Gnomad4 EAS exome
AF:
0.160
Gnomad4 SAS exome
AF:
0.0739
Gnomad4 FIN exome
AF:
0.0773
Gnomad4 NFE exome
AF:
0.0785
Gnomad4 OTH exome
AF:
0.0841
GnomAD4 genome
AF:
0.0787
AC:
11986
AN:
152258
Hom.:
810
Cov.:
33
AF XY:
0.0815
AC XY:
6065
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0198
Gnomad4 AMR
AF:
0.211
Gnomad4 ASJ
AF:
0.0559
Gnomad4 EAS
AF:
0.151
Gnomad4 SAS
AF:
0.0677
Gnomad4 FIN
AF:
0.0766
Gnomad4 NFE
AF:
0.0818
Gnomad4 OTH
AF:
0.0933
Alfa
AF:
0.0779
Hom.:
127
Bravo
AF:
0.0904
Asia WGS
AF:
0.122
AC:
425
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
12
DANN
Benign
0.57
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.25
Position offset: -19

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: rs1805312; hg19: chr9-116152990; API