2-73385903-TGGAGGAGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGA

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001378454.1(ALMS1):c.69_74delGGAGGA(p.Glu24_Glu25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 700,128 control chromosomes in the GnomAD database, including 21,830 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E23E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.39 ( 12811 hom., cov: 0)

Exomes 𝑓: 0.27 ( 9019 hom. )

Consequence

ALMS1
NM_001378454.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.21

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

Alstrom syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp

ALMS1 links:

ENSG00000285068 (HGNC:):

ENSG00000285068 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001378454.1

BP6

Variant 2-73385903-TGGAGGA-T is Benign according to our data. Variant chr2-73385903-TGGAGGA-T is described in ClinVar as Benign. ClinVar VariationId is 221075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1 link	c.69_74delGGAGGA	p.Glu24_Glu25del	disruptive_inframe_deletion	Exon 1 of 23	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 link	c.69_74delGGAGGA	p.Glu24_Glu25del	disruptive_inframe_deletion	Exon 1 of 23		NP_055935.4	Q8TCU4
LOC105374804	XR_007087045.1 link	n.-228_-223delTCCTCC		upstream_gene_variant
LOC105374804	XR_007087053.1 link	n.-228_-223delTCCTCC		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 link	c.69_74delGGAGGA	p.Glu24_Glu25del	disruptive_inframe_deletion	Exon 1 of 23	1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

56506

AN:

143428

Hom.:

12779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.254

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.354

GnomAD2 exomes

AF:

0.286

AC:

23877

AN:

83366

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.613

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.265

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.268

AC:

148993

AN:

556596

Hom.:

9019

AF XY:

0.265

AC XY:

78880

AN XY:

297226

show subpopulations

African (AFR)

AF:

0.514

AC:

8079

AN:

15706

American (AMR)

AF:

0.246

AC:

7557

AN:

30756

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

4105

AN:

17630

East Asian (EAS)

AF:

0.213

AC:

6516

AN:

30630

South Asian (SAS)

AF:

0.245

AC:

13691

AN:

55906

European-Finnish (FIN)

AF:

0.245

AC:

8884

AN:

36252

Middle Eastern (MID)

AF:

0.250

AC:

605

AN:

2418

European-Non Finnish (NFE)

AF:

0.271

AC:

91429

AN:

337232

Other (OTH)

AF:

0.270

AC:

8127

AN:

30066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

5769

11538

17307

23076

28845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1070

2140

3210

4280

5350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.394

AC:

56594

AN:

143532

Hom.:

12811

Cov.:

AF XY:

0.389

AC XY:

27093

AN XY:

69610

show subpopulations

African (AFR)

AF:

0.648

AC:

25889

AN:

39930

American (AMR)

AF:

0.308

AC:

4526

AN:

14678

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

905

AN:

3322

East Asian (EAS)

AF:

0.204

AC:

937

AN:

4584

South Asian (SAS)

AF:

0.284

AC:

1210

AN:

4258

European-Finnish (FIN)

AF:

0.272

AC:

2551

AN:

9392

Middle Eastern (MID)

AF:

0.257

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.304

AC:

19552

AN:

64298

Other (OTH)

AF:

0.353

AC:

697

AN:

1972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1460

2920

4381

5841

7301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.237

Hom.:

1022

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 04, 2018

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Alstrom syndrome

Benign:3

Jun 06, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 16, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24122612, 25468891) -

Cardiovascular phenotype

Benign:1

Nov 19, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

Mutation Taster

=197/3

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over