Variant 2-73385823-TC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The ENST00000484298.5(ALMS1):c.-39del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 658,344 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 3 hom. )

Consequence

ALMS1
ENST00000484298.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.98

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]

ALMS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00292 (424/145020) while in subpopulation NFE AF= 0.00505 (333/65924). AF 95% confidence interval is 0.0046. There are 1 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALMS1	NM_015120.4 linkuse as main transcript	c.-39del		5_prime_UTR_variant	1/23
ALMS1	NM_001378454.1 linkuse as main transcript			upstream_gene_variant		ENST00000613296.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000484298.5 linkuse as main transcript	c.-39del	5_prime_UTR_variant	1/22	1		A2
ALMS1	ENST00000613296.6 linkuse as main transcript		upstream_gene_variant		1	NM_001378454.1	P3	Q8TCU4-1
ALMS1	ENST00000614410.4 linkuse as main transcript		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

424

AN:

144946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000668

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00117

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00294

Gnomad FIN

AF:

0.00310

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00505

Gnomad OTH

AF:

0.00201

GnomAD3 exomes

AF:

0.00211

AC:

182

AN:

86338

Hom.:

AF XY:

0.00199

AC XY:

AN XY:

46172

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.000959

Gnomad ASJ exome

AF:

0.000211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00191

Gnomad FIN exome

AF:

0.00326

Gnomad NFE exome

AF:

0.00380

Gnomad OTH exome

AF:

0.00220

GnomAD4 exome

AF:

0.00330

AC:

1695

AN:

513324

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

913

AN XY:

276154

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.000945

Gnomad4 ASJ exome

AF:

0.000173

Gnomad4 EAS exome

AF:

0.0000327

Gnomad4 SAS exome

AF:

0.00217

Gnomad4 FIN exome

AF:

0.00310

Gnomad4 NFE exome

AF:

0.00444

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.00292

AC:

424

AN:

145020

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

185

AN XY:

70452

show subpopulations

Gnomad4 AFR

AF:

0.000666

Gnomad4 AMR

AF:

0.00117

Gnomad4 ASJ

AF:

0.000293

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00295

Gnomad4 FIN

AF:

0.00310

Gnomad4 NFE

AF:

0.00505

Gnomad4 OTH

AF:

0.00199

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Alstrom syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over