chr2-73601183-T-C

Position:

chr2-73601183-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000613296.6(ALMS1):c.11873-12T>C variant causes a splice polypyrimidine tract, 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
ENST00000613296.6 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.33

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 -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 id 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/exons	MANE	Protein	UniProt
ALMS1	NM_001378454.1 linkuse as main transcript	c.11873-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 linkuse as main transcript	c.11873-12T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 linkuse as main transcript	c.11873-12T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001378454.1	ENSP00000482968	P3	Q8TCU4-1

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

GnomAD3 exomes

AF:

0.635

AC:

158858

AN:

250274

Hom.:

52200

AF XY:

0.639

AC XY:

86686

AN XY:

135728

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 SAS exome

AF:

0.673

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

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.710

Gnomad4 ASJ exome

AF:

0.682

Gnomad4 EAS exome

AF:

0.734

Gnomad4 SAS exome

AF:

0.667

Gnomad4 FIN exome

AF:

0.632

Gnomad4 NFE exome

AF:

0.632

Gnomad4 OTH exome

AF:

0.632

GnomAD4 genome

AF:

0.529

AC:

80512

AN:

152134

Hom.:

23968

Cov.:

AF XY:

0.536

AC XY:

39893

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.646

Gnomad4 ASJ

AF:

0.667

Gnomad4 EAS

AF:

0.745

Gnomad4 SAS

AF:

0.677

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.632

Gnomad4 OTH

AF:

0.567

Alfa

AF:

0.593

Hom.:

5150

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

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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 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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 21, 2016	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). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Alstrom syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.44

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

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