Variant chr2-73385903-TGGA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001378454.1(ALMS1):c.72_74del(p.Glu28del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 698,502 control chromosomes in the GnomAD database, including 613 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 348 hom., cov: 0)

Exomes 𝑓: 0.034 ( 265 hom. )

Consequence

ALMS1
NM_001378454.1 inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: 3.18

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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001378454.1

BP6

Variant 2-73385903-TGGA-T is Benign according to our data. Variant chr2-73385903-TGGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 193378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALMS1	NM_001378454.1 linkuse as main transcript	c.72_74del	p.Glu28del	inframe_deletion	1/23	ENST00000613296.6
ALMS1	NM_015120.4 linkuse as main transcript	c.72_74del	p.Glu29del	inframe_deletion	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000613296.6 linkuse as main transcript	c.72_74del	p.Glu28del	inframe_deletion	1/23	1	NM_001378454.1	P3	Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.0546

AC:

7831

AN:

143476

Hom.:

344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0949

Gnomad AMI

AF:

0.0170

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0316

Gnomad EAS

AF:

0.0424

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.0458

Gnomad MID

AF:

0.0142

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0631

AC:

5258

AN:

83366

Hom.:

225

AF XY:

0.0545

AC XY:

2380

AN XY:

43654

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.0365

Gnomad EAS exome

AF:

0.0407

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.0392

Gnomad NFE exome

AF:

0.0252

Gnomad OTH exome

AF:

0.0560

GnomAD4 exome

AF:

0.0343

AC:

19023

AN:

554922

Hom.:

265

AF XY:

0.0323

AC XY:

9565

AN XY:

296246

show subpopulations

Gnomad4 AFR exome

AF:

0.0885

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.0327

Gnomad4 EAS exome

AF:

0.0352

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0403

Gnomad4 NFE exome

AF:

0.0234

Gnomad4 OTH exome

AF:

0.0371

GnomAD4 genome

AF:

0.0547

AC:

7850

AN:

143580

Hom.:

348

Cov.:

AF XY:

0.0555

AC XY:

3865

AN XY:

69632

show subpopulations

Gnomad4 AFR

AF:

0.0949

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0316

Gnomad4 EAS

AF:

0.0423

Gnomad4 SAS

AF:

0.0134

Gnomad4 FIN

AF:

0.0458

Gnomad4 NFE

AF:

0.0233

Gnomad4 OTH

AF:

0.0456

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 12, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Mar 18, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	Feb 11, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 05, 2015	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 04, 2013	- -

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2016	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Alstrom syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Genetics, Royal Melbourne Hospital	Jul 07, 2023	- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 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

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