rs13391552

Positions:

• chr2-73591809-G-A
• chr2-73591809-G-C
• chr2-73591809-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378454.1(ALMS1):​c.11548-7592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,006 control chromosomes in the GnomAD database, including 9,048 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9048 hom., cov: 32)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALMS1	NM_001378454.1	c.11548-7592G>A		intron_variant		ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4	c.11548-7592G>A		intron_variant			NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6	c.11548-7592G>A		intron_variant		1	NM_001378454.1	ENSP00000482968	P3

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46726 AN: 151888 Hom.: 9013 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.308 AC: 46815 AN: 152006 Hom.: 9048 Cov.: 32 AF XY: 0.301 AC XY: 22405 AN XY: 74312

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.00443

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.282

Alfa AF: 0.224 Hom.: 7582

Bravo AF: 0.322

Asia WGS AF: 0.108 AC: 375 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.88
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs13391552; hg19: chr2-73818936;