Variant chr2-73385903-T-TGGA 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_74dup(p.Glu27dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12015 hom., cov: 0)

Exomes 𝑓: 0.35 ( 3279 hom. )

Consequence

ALMS1
NM_001378454.1 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.369

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:

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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-T-TGGA is Benign according to our data. Variant chr2-73385903-T-TGGA is described in ClinVar as [Benign]. Clinvar id is 1206378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 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_74dup	p.Glu27dup	inframe_insertion	1/23	ENST00000613296.6
ALMS1	NM_015120.4 linkuse as main transcript	c.72_74dup	p.Glu27dup	inframe_insertion	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000613296.6 linkuse as main transcript	c.72_74dup	p.Glu27dup	inframe_insertion	1/23	1	NM_001378454.1	P3	Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

54301

AN:

143200

Hom.:

12021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.518

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.415

GnomAD3 exomes

AF:

0.312

AC:

26026

AN:

83366

Hom.:

803

AF XY:

0.314

AC XY:

13691

AN XY:

43654

show subpopulations

Gnomad AFR exome

AF:

0.0853

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.418

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.347

AC:

192548

AN:

554346

Hom.:

3279

Cov.:

AF XY:

0.348

AC XY:

102997

AN XY:

295878

show subpopulations

Gnomad4 AFR exome

AF:

0.0931

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.354

GnomAD4 genome

AF:

0.379

AC:

54294

AN:

143306

Hom.:

12015

Cov.:

AF XY:

0.380

AC XY:

26431

AN XY:

69494

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.393

Gnomad4 ASJ

AF:

0.513

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.477

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.496

Gnomad4 OTH

AF:

0.416

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Alstrom syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Molecular Genetics, Royal Melbourne Hospital	Jul 07, 2023	- -
Benign, criteria provided, single submitter	research	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	Dec 12, 2023	- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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