rs11884776

Positions:

chr2-73519796-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378454.1(ALMS1):c.9561C>T(p.Thr3187=) 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

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 Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ALMS1	NM_001378454.1 linkuse as main transcript	c.9561C>T	p.Thr3187=	synonymous_variant	11/23	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 linkuse as main transcript	c.9564C>T	p.Thr3188=	synonymous_variant	11/23		NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 linkuse as main transcript	c.9561C>T	p.Thr3187=	synonymous_variant	11/23	1	NM_001378454.1	ENSP00000482968	P3	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

GnomAD3 exomes

AF:

0.212

AC:

52902

AN:

249110

Hom.:

6860

AF XY:

0.206

AC XY:

27836

AN XY:

135178

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 SAS exome

AF:

0.156

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

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.00413

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.213

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.293

AC:

44502

AN:

151990

Hom.:

7829

Cov.:

AF XY:

0.287

AC XY:

21323

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.498

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.270

Alfa

AF:

0.235

Hom.:

8450

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	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). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 09, 2016	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

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2018

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.33

DANN

Benign

0.91

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