rs6546857

chr2-73610828-A-G

Variant summary

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

The ENST00000651434.1(ALMS1):c.*2996+1146A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,188 control chromosomes in the GnomAD database, including 9,175 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 (9172 hom., cov: 32)
  • Exomes 𝑓: 0.60 (3 hom.)
• Consequence: ALMS1 ENST00000651434.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 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.*2996+1146A>G		intron_variant, NMD_transcript_variant
ALMS1	ENST00000490821.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47518 AN: 152050 Hom.: 9138 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.600 AC: 12 AN: 20 Hom.: 3 Cov.: 0 AF XY: 0.563 AC XY: 9 AN XY: 16

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 0.556

GnomAD4 genome AF: 0.313 AC: 47607 AN: 152168 Hom.: 9172 Cov.: 32 AF XY: 0.307 AC XY: 22808 AN XY: 74398

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.287

Alfa AF: 0.299 Hom.: 1217

Bravo AF: 0.325

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	12
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6546857; hg19: chr2-73837955;