rs1881245

Positions:

• chr2-73422800-G-A
• chr2-73422800-G-C
• chr2-73422800-G-T

Variant summary

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

The NM_001378454.1(ALMS1):​c.647-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,349,096 control chromosomes in the GnomAD database, including 52,567 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 0.36 (13269 hom., cov: 31)
  • Exomes 𝑓: 0.24 (39298 hom.)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALMS1	NM_001378454.1	c.647-57G>A		intron_variant		ENST00000613296.6
ALMS1	NM_015120.4	c.647-57G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000613296.6	c.647-57G>A		intron_variant		1	NM_001378454.1	P3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54702 AN: 151686 Hom.: 13213 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00713

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.238 AC: 285528 AN: 1197294 Hom.: 39298 AF XY: 0.234 AC XY: 142155 AN XY: 608516

Gnomad4 AFR exome AF: 0.697

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.0122

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.361 AC: 54817 AN: 151802 Hom.: 13269 Cov.: 31 AF XY: 0.355 AC XY: 26306 AN XY: 74164

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00715

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.316

Alfa AF: 0.240 Hom.: 5808

Bravo AF: 0.386

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1881245; hg19: chr2-73649928;