rs6745480

chr2-73612928-G-Achr2-73612928-G-T

Variant summary

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

The ENST00000651434.1(ALMS1):c.*2997-2339G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,926 control chromosomes in the GnomAD database, including 15,043 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 0.38 (15043 hom., cov: 31)
• Consequence: ALMS1 ENST00000651434.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000651434.1	c.*2997-2339G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57449 AN: 151808 Hom.: 14987 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.00695

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.379 AC: 57568 AN: 151926 Hom.: 15043 Cov.: 31 AF XY: 0.373 AC XY: 27642 AN XY: 74206

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.00697

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.327

Alfa AF: 0.342 Hom.: 1858

Bravo AF: 0.406

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6745480; hg19: chr2-73840055;