rs181226362

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001378454.1(ALMS1):ā€‹c.8274A>Gā€‹(p.Gln2758Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,614,138 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0013 ( 1 hom., cov: 32)
Exomes š‘“: 0.00013 ( 0 hom. )

Consequence

ALMS1
NM_001378454.1 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.198
Variant links:
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 -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 2-73490233-A-G is Benign according to our data. Variant chr2-73490233-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 459891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.198 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00129 (197/152294) while in subpopulation AFR AF= 0.00443 (184/41550). AF 95% confidence interval is 0.00391. There are 1 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALMS1NM_001378454.1 linkuse as main transcriptc.8274A>G p.Gln2758Gln synonymous_variant 10/23 ENST00000613296.6 NP_001365383.1
ALMS1NM_015120.4 linkuse as main transcriptc.8274A>G p.Gln2758Gln synonymous_variant 10/23 NP_055935.4 Q8TCU4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALMS1ENST00000613296.6 linkuse as main transcriptc.8274A>G p.Gln2758Gln synonymous_variant 10/231 NM_001378454.1 ENSP00000482968.1 Q8TCU4-1

Frequencies

GnomAD3 genomes
AF:
0.00129
AC:
197
AN:
152176
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00444
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000337
AC:
84
AN:
248934
Hom.:
0
AF XY:
0.000266
AC XY:
36
AN XY:
135092
show subpopulations
Gnomad AFR exome
AF:
0.00453
Gnomad AMR exome
AF:
0.000319
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.000125
AC:
183
AN:
1461844
Hom.:
0
Cov.:
32
AF XY:
0.0000853
AC XY:
62
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00445
Gnomad4 AMR exome
AF:
0.000335
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.00129
AC:
197
AN:
152294
Hom.:
1
Cov.:
32
AF XY:
0.00133
AC XY:
99
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00443
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000818
Hom.:
0
Bravo
AF:
0.00150

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022ALMS1: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 05, 2021- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpSep 29, 2024- -
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 01, 2019This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Alstrom syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
1.4
DANN
Benign
0.77

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: rs181226362; hg19: chr2-73717360; API