chr2-73612928-G-A

Variant names:

• chr2-73612928-G-A
• rs6745480
• ENST00000651434.1:n.*2997-2339G>A

Variant summary

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

The ENST00000651434.1(ALMS1):​n.*2997-2339G>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 11 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=-0.91).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000651434.1	n.*2997-2339G>A		intron_variant	Intron 15 of 16			ENSP00000498259.1

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

African (AFR) AF: 0.742 AC: 30765 AN: 41444

American (AMR) AF: 0.369 AC: 5642 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3468

East Asian (EAS) AF: 0.00697 AC: 36 AN: 5168

South Asian (SAS) AF: 0.149 AC: 718 AN: 4804

European-Finnish (FIN) AF: 0.243 AC: 2554 AN: 10512

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.240 AC: 16291 AN: 67942

Other (OTH) AF: 0.327 AC: 691 AN: 2110

Alfa AF: 0.479 Hom.: 5540

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
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs6745480; hg19: chr2-73840055;