rs10199680
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001378454.1(ALMS1):c.9782-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 1,612,400 control chromosomes in the GnomAD database, including 556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.034 ( 292 hom., cov: 33)
Exomes 𝑓: 0.0035 ( 264 hom. )
Consequence
ALMS1
NM_001378454.1 splice_polypyrimidine_tract, intron
NM_001378454.1 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.183
Genes affected
ALMS1 (HGNC:428): (ALMS1 centrosome and basal body associated protein) This gene encodes a protein containing a large tandem-repeat domain as well as additional low complexity regions. The encoded protein functions in microtubule organization, particularly in the formation and maintanance of cilia. Mutations in this gene cause Alstrom syndrome. There is a pseudogene for this gene located adjacent in the same region of chromosome 2. Alternative splice variants have been described but their full length nature has not been determined. [provided by RefSeq, Apr 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 2-73534815-C-T is Benign according to our data. Variant chr2-73534815-C-T is described in ClinVar as [Benign]. Clinvar id is 387349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.9782-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000613296.6 | |||
ALMS1 | NM_015120.4 | c.9782-9C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.9782-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001378454.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0336 AC: 5110AN: 152034Hom.: 287 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
5110
AN:
152034
Hom.:
Cov.:
33
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: 0.00869 AC: 2165AN: 249192Hom.: 126 AF XY: 0.00621 AC XY: 840AN XY: 135208
GnomAD3 exomes
AF:
AC:
2165
AN:
249192
Hom.:
AF XY:
AC XY:
840
AN XY:
135208
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: 0.00353 AC: 5152AN: 1460248Hom.: 264 Cov.: 31 AF XY: 0.00303 AC XY: 2201AN XY: 726562
GnomAD4 exome
AF:
AC:
5152
AN:
1460248
Hom.:
Cov.:
31
AF XY:
AC XY:
2201
AN XY:
726562
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: 0.0338 AC: 5144AN: 152152Hom.: 292 Cov.: 33 AF XY: 0.0329 AC XY: 2447AN XY: 74382
GnomAD4 genome
?
AF:
AC:
5144
AN:
152152
Hom.:
Cov.:
33
AF XY:
AC XY:
2447
AN XY:
74382
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:
35
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 10, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | c.9779-9C>T in intron 11 of ALMS1: This variant is not expected to have clinical significance because a C>T change at this position does not diverge from the sp lice consensus sequence and is therefore unlikely to impact splicing. It has bee n identified in 12.00% (1176/9796) of African chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs10199680). - |
Alstrom syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 23, 2018 | - - |
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at