ENST00000651434.1:n.*2996+1146A>G

Variant names:

• chr2-73610828-A-G
• rs6546857
• ENST00000651434.1:n.*2996+1146A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000651434.1(ALMS1):​n.*2996+1146A>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 25 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 Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651434.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000651434.1		n.*2996+1146A>G		intron	N/A	ENSP00000498259.1
	ALMS1	ENST00000490821.1	TSL:5	n.*35A>G		downstream_gene	N/A

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.556 AC: 10 AN: 18

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.543 AC: 22529 AN: 41484

American (AMR) AF: 0.263 AC: 4028 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5184

South Asian (SAS) AF: 0.146 AC: 707 AN: 4826

European-Finnish (FIN) AF: 0.234 AC: 2478 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16410 AN: 67994

Other (OTH) AF: 0.287 AC: 606 AN: 2112

Alfa AF: 0.269 Hom.: 10533

Bravo AF: 0.325

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs6546857; hg19: chr2-73837955;