rs543687863

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The NM_015120.4(ALMS1):​c.-48C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 680,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ALMS1
NM_015120.4 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.134
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 Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000657 (100/152130) while in subpopulation AFR AF= 0.00188 (78/41554). AF 95% confidence interval is 0.00154. There are 0 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALMS1NM_015120.4 linkc.-48C>G 5_prime_UTR_variant Exon 1 of 23 NP_055935.4 Q8TCU4
ALMS1NM_001378454.1 linkc.-48C>G upstream_gene_variant ENST00000613296.6 NP_001365383.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALMS1ENST00000484298 linkc.-48C>G 5_prime_UTR_variant Exon 1 of 22 1 ENSP00000478155.1 A0A087WTU9
ALMS1ENST00000613296.6 linkc.-48C>G upstream_gene_variant 1 NM_001378454.1 ENSP00000482968.1 Q8TCU4-1
ALMS1ENST00000614410.4 linkc.-48C>G upstream_gene_variant 5 ENSP00000479094.1 A0A087WV20

Frequencies

GnomAD3 genomes
AF:
0.000664
AC:
101
AN:
152026
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00191
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00137
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000188
AC:
19
AN:
100932
Hom.:
0
AF XY:
0.000167
AC XY:
9
AN XY:
53742
show subpopulations
Gnomad AFR exome
AF:
0.00201
Gnomad AMR exome
AF:
0.000369
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:
0.00
Gnomad OTH exome
AF:
0.000306
GnomAD4 exome
AF:
0.000127
AC:
67
AN:
528710
Hom.:
0
Cov.:
5
AF XY:
0.000102
AC XY:
29
AN XY:
284466
show subpopulations
Gnomad4 AFR exome
AF:
0.00234
Gnomad4 AMR exome
AF:
0.000339
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000354
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000969
Gnomad4 OTH exome
AF:
0.000506
GnomAD4 genome
AF:
0.000657
AC:
100
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.000699
AC XY:
52
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00188
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.000763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
9.3
DANN
Benign
0.63

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: rs543687863; hg19: chr2-73612949; API