Variant rs34628045 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_001378454.1(ALMS1):c.1574_1576delCTC(p.Pro525del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,613,222 control chromosomes in the GnomAD database, including 114,241 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15344 hom., cov: 0)

Exomes 𝑓: 0.36 ( 98897 hom. )

Consequence

ALMS1
NM_001378454.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.58

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 -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001378454.1. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 2-73448097-TCTC-T is Benign according to our data. Variant chr2-73448097-TCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 210124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 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.1574_1576delCTC	p.Pro525del	disruptive_inframe_deletion	8/23	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4 linkuse as main transcript	c.1574_1576delCTC	p.Pro525del	disruptive_inframe_deletion	8/23		NP_055935.4	Q8TCU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 linkuse as main transcript	c.1574_1576delCTC	p.Pro525del	disruptive_inframe_deletion	8/23	1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65206

AN:

151534

Hom.:

15308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.638

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.405

GnomAD4 exome

AF:

0.363

AC:

531038

AN:

1461570

Hom.:

98897

AF XY:

0.363

AC XY:

263686

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.654

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.369

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.367

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.431

AC:

65303

AN:

151652

Hom.:

15344

Cov.:

AF XY:

0.425

AC XY:

31473

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.639

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.378

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.404

Alfa

AF:

0.213

Hom.:

2755

Bravo

AF:

0.438

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 06, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 22, 2023	The p.Pro525del variant in ALMS1 is classified as benign because it has been identified in 63.8% (26295/41186) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2019

- -

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