Genetic Variant ALMS1:c.-27_-25dupCTC (chr2-73385828-C-CCCT) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001378454.1(ALMS1):c.-27_-25dupCTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000977 in 665,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

ALMS1
NM_001378454.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.530

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Alstrom syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp

ALMS1 links:

ENSG00000285068 (HGNC:):

ENSG00000285068 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 2-73385828-C-CCCT is Benign according to our data. Variant chr2-73385828-C-CCCT is described in ClinVar as [Benign]. Clinvar id is 421812.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1 link	c.-27_-25dupCTC		5_prime_UTR_variant	Exon 1 of 23	ENST00000613296.6	NP_001365383.1
ALMS1	NM_001378454.1 link	c.-41_-40insCCT		upstream_gene_variant		ENST00000613296.6	NP_001365383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 link	c.-27_-25dupCTC		5_prime_UTR_variant	Exon 1 of 23	1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1
ALMS1	ENST00000613296.6 link	c.-41_-40insCCT		upstream_gene_variant		1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000885

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000157

AC:

AN:

69986

AF XY:

0.000240

show subpopulations

Gnomad AFR exome

AF:

0.000664

Gnomad AMR exome

AF:

0.000283

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000393

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000857

AC:

AN:

513370

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

276450

show subpopulations

African (AFR)

AF:

0.000279

AC:

AN:

14360

American (AMR)

AF:

0.000279

AC:

AN:

32290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17782

East Asian (EAS)

AF:

0.0000333

AC:

AN:

30044

South Asian (SAS)

AF:

0.000196

AC:

AN:

56232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2272

European-Non Finnish (NFE)

AF:

0.0000535

AC:

AN:

299050

Other (OTH)

AF:

0.000105

AC:

AN:

28472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000138

AC:

AN:

151768

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41514

American (AMR)

AF:

0.000131

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000195

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000885

AC:

AN:

67808

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 05, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-73385828-C-CCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over