ENST00000484298.5:c.-45C>G

Variant names:

• chr2-73385824-C-G
• rs539250179
• ENST00000484298.5:c.-45C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000484298.5(ALMS1):​c.-45C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALMS1 ENST00000484298.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98
• Publications: 0 publications found

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, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ENSG00000285068 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-73385824-C-G is Benign according to our data. Variant chr2-73385824-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 390301.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000484298.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	NM_015120.4		c.-45C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	NP_055935.4	Q8TCU4
	ALMS1	NM_015120.4		c.-45C>G		5_prime_UTR	Exon 1 of 23	NP_055935.4	Q8TCU4
	ALMS1	NM_001378454.1	MANE Select	c.-45C>G		upstream_gene	N/A	NP_001365383.1	Q8TCU4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000484298.5	TSL:1	c.-45C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	ENSP00000478155.1	A0A087WTU9
	ALMS1	ENST00000484298.5	TSL:1	c.-45C>G		5_prime_UTR	Exon 1 of 22	ENSP00000478155.1	A0A087WTU9
	ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.-45C>G		upstream_gene	N/A	ENSP00000482968.1	Q8TCU4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 527720 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 284168

African (AFR) AF: 0.00 AC: 0 AN: 14864

American (AMR) AF: 0.00 AC: 0 AN: 32542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18280

East Asian (EAS) AF: 0.00 AC: 0 AN: 31262

South Asian (SAS) AF: 0.00 AC: 0 AN: 56878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2358

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 307990

Other (OTH) AF: 0.00 AC: 0 AN: 29560

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.86
DANN	Benign	0.57
PhyloP100		-2.0
PromoterAI		-0.046	Neutral

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

Other links and lift over

dbSNP: rs539250179; hg19: chr2-73612952;