rs11884776

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378454.1(ALMS1):c.9561C>T(p.Thr3187Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,613,364 control chromosomes in the GnomAD database, including 46,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7829 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38652 hom. )

Consequence

ALMS1
NM_001378454.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.746

Publications

34 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-73519796-C-T is Benign according to our data. Variant chr2-73519796-C-T is described in ClinVar as Benign. ClinVar VariationId is 383763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.746 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1 link	c.9561C>T	p.Thr3187Thr	synonymous_variant	Exon 11 of 23	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 link	c.9561C>T	p.Thr3187Thr	synonymous_variant	Exon 11 of 23		NP_055935.4	Q8TCU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 link	c.9561C>T	p.Thr3187Thr	synonymous_variant	Exon 11 of 23	1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44421

AN:

151872

Hom.:

7802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.274

GnomAD2 exomes

AF:

0.212

AC:

52902

AN:

249110

AF XY:

0.206

show subpopulations

Gnomad AFR exome

AF:

0.508

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.00412

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.221

AC:

323283

AN:

1461374

Hom.:

38652

Cov.:

AF XY:

0.219

AC XY:

159166

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.502

AC:

16788

AN:

33444

American (AMR)

AF:

0.223

AC:

9973

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3651

AN:

26124

East Asian (EAS)

AF:

0.00413

AC:

164

AN:

39682

South Asian (SAS)

AF:

0.163

AC:

14032

AN:

86220

European-Finnish (FIN)

AF:

0.213

AC:

11358

AN:

53402

Middle Eastern (MID)

AF:

0.221

AC:

1273

AN:

5766

European-Non Finnish (NFE)

AF:

0.228

AC:

253005

AN:

1111648

Other (OTH)

AF:

0.216

AC:

13039

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

13045

26090

39134

52179

65224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8584

17168

25752

34336

42920

<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:

0.293

AC:

44502

AN:

151990

Hom.:

7829

Cov.:

AF XY:

0.287

AC XY:

21323

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.498

AC:

20627

AN:

41438

American (AMR)

AF:

0.253

AC:

3861

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

514

AN:

3468

East Asian (EAS)

AF:

0.00444

AC:

AN:

5182

South Asian (SAS)

AF:

0.145

AC:

700

AN:

4818

European-Finnish (FIN)

AF:

0.222

AC:

2339

AN:

10554

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15606

AN:

67952

Other (OTH)

AF:

0.270

AC:

571

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.244

Hom.:

17969

Bravo

AF:

0.304

Asia WGS

AF:

0.100

AC:

347

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.226

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Thr3186Thr in exon 11 of ALMS1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 57.41% (759/1322) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs11884776). -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

Alstrom syndrome

Benign:3

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

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cardiovascular phenotype

Benign:1

Dec 21, 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

AlphaMissense

Benign

0.076

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.33

(source)

DANN

Benign

0.91

PhyloP100

-0.75

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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