Variant 2-73385828-CCCT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The ENST00000484298.5(ALMS1):c.-27_-25del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 386,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALMS1
ENST00000484298.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.312

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 2-73385828-CCCT-C is Benign according to our data. Variant chr2-73385828-CCCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 337004.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0245 (9465/386836) while in subpopulation AFR AF= 0.0313 (349/11166). AF 95% confidence interval is 0.0286. There are 0 homozygotes in gnomad4_exome. There are 4815 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALMS1	NM_015120.4 linkuse as main transcript	c.-27_-25del		5_prime_UTR_variant	1/23		NP_055935.4
ALMS1	NM_001378454.1 linkuse as main transcript			upstream_gene_variant		ENST00000613296.6	NP_001365383.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000484298.5 linkuse as main transcript	c.-27_-25del	5_prime_UTR_variant	1/22	1		ENSP00000478155	A2
ALMS1	ENST00000613296.6 linkuse as main transcript		upstream_gene_variant		1	NM_001378454.1	ENSP00000482968	P3	Q8TCU4-1
ALMS1	ENST00000614410.4 linkuse as main transcript		upstream_gene_variant		5		ENSP00000479094

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151496

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0245

AC:

9465

AN:

386836

Hom.:

AF XY:

0.0231

AC XY:

4815

AN XY:

208532

show subpopulations

Gnomad4 AFR exome

AF:

0.0313

Gnomad4 AMR exome

AF:

0.0244

Gnomad4 ASJ exome

AF:

0.0282

Gnomad4 EAS exome

AF:

0.0270

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.0251

Gnomad4 OTH exome

AF:

0.0265

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000396

AC:

AN:

151596

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0148

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Alstrom syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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