2-73601183-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378454.1(ALMS1):c.11873-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,613,652 control chromosomes in the GnomAD database, including 318,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23968 hom., cov: 33)

Exomes 𝑓: 0.63 ( 294586 hom. )

Consequence

ALMS1
NM_001378454.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.33

Publications

18 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 2-73601183-T-C is Benign according to our data. Variant chr2-73601183-T-C is described in ClinVar as Benign. ClinVar VariationId is 383770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1 link	c.11873-12T>C		intron_variant	Intron 18 of 22	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 link	c.11873-12T>C		intron_variant	Intron 18 of 22		NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 link	c.11873-12T>C		intron_variant	Intron 18 of 22	1	NM_001378454.1	ENSP00000482968.1

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80501

AN:

152014

Hom.:

23970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.677

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.667

Gnomad EAS

AF:

0.745

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.567

GnomAD2 exomes

AF:

0.635

AC:

158858

AN:

250274

AF XY:

0.639

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.722

Gnomad ASJ exome

AF:

0.683

Gnomad EAS exome

AF:

0.757

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.630

AC:

921376

AN:

1461518

Hom.:

294586

Cov.:

AF XY:

0.632

AC XY:

459391

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.210

AC:

7043

AN:

33474

American (AMR)

AF:

0.710

AC:

31751

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

17837

AN:

26136

East Asian (EAS)

AF:

0.734

AC:

29134

AN:

39698

South Asian (SAS)

AF:

0.667

AC:

57398

AN:

86074

European-Finnish (FIN)

AF:

0.632

AC:

33757

AN:

53414

Middle Eastern (MID)

AF:

0.617

AC:

3557

AN:

5766

European-Non Finnish (NFE)

AF:

0.632

AC:

702732

AN:

1111856

Other (OTH)

AF:

0.632

AC:

38167

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

20149

40298

60446

80595

100744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18670

37340

56010

74680

93350

<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:

0.529

AC:

80512

AN:

152134

Hom.:

23968

Cov.:

AF XY:

0.536

AC XY:

39893

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.231

AC:

9575

AN:

41508

American (AMR)

AF:

0.646

AC:

9876

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

2314

AN:

3470

East Asian (EAS)

AF:

0.745

AC:

3851

AN:

5168

South Asian (SAS)

AF:

0.677

AC:

3267

AN:

4828

European-Finnish (FIN)

AF:

0.629

AC:

6656

AN:

10574

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.632

AC:

42968

AN:

67976

Other (OTH)

AF:

0.567

AC:

1200

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1723

3446

5169

6892

8615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.592

Hom.:

9131

Bravo

AF:

0.517

Asia WGS

AF:

0.695

AC:

2418

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Sep 09, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.11870-12T>C in intron 18 of ALMS1: This variant is not expected to have clinic al significance because a T>C change at this position does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. It has b een identified in 75.28% (6509/8646) of East Asian chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1320374). -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Alstrom syndrome

Benign:2

Jul 14, 2021

Genome-Nilou Lab

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.44

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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