rs9813468

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000484952.6(ALAS1):​c.1600-244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 152,328 control chromosomes in the GnomAD database, including 31 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 0.011 ( 31 hom., cov: 32)

Consequence

ALAS1
ENST00000484952.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.57
Variant links:
Genes affected
ALAS1 (HGNC:396): (5'-aminolevulinate synthase 1) This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1722/152328) while in subpopulation AFR AF= 0.0386 (1606/41578). AF 95% confidence interval is 0.0371. There are 31 homozygotes in gnomad4. There are 816 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALAS1NM_000688.6 linkuse as main transcriptc.1600-244G>A intron_variant ENST00000484952.6 NP_000679.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALAS1ENST00000484952.6 linkuse as main transcriptc.1600-244G>A intron_variant 1 NM_000688.6 ENSP00000418779 P1P13196-1

Frequencies

GnomAD3 genomes
AF:
0.0113
AC:
1718
AN:
152210
Hom.:
31
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0386
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.0105
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0113
AC:
1722
AN:
152328
Hom.:
31
Cov.:
32
AF XY:
0.0110
AC XY:
816
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0386
Gnomad4 AMR
AF:
0.00418
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00316
Hom.:
5
Bravo
AF:
0.0135
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.064
DANN
Benign
0.51

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: rs9813468; hg19: chr3-52246030; API