2-73516855-A-G

Position:

• chr2-73516855-A-G

Variant summary

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

The NM_001378454.1(ALMS1):​c.9540-2920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,960 control chromosomes in the GnomAD database, including 8,280 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 0.30 (8280 hom., cov: 32)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALMS1	NM_001378454.1	c.9540-2920A>G		intron_variant		ENST00000613296.6
ALMS1	NM_015120.4	c.9540-2920A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000613296.6	c.9540-2920A>G		intron_variant		1	NM_001378454.1	P3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45395 AN: 151842 Hom.: 8244 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.299 AC: 45486 AN: 151960 Hom.: 8280 Cov.: 32 AF XY: 0.293 AC XY: 21784 AN XY: 74252

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.278

Alfa AF: 0.236 Hom.: 4679

Bravo AF: 0.312

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.93

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: rs9309473; hg19: chr2-73743982;