rs6546847

chr2-73558231-A-Gchr2-73558231-A-T

Variant summary

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

The NM_001378454.1(ALMS1):c.10214-741A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,106 control chromosomes in the GnomAD database, including 15,948 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 0.39 (15948 hom., cov: 32)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALMS1	NM_001378454.1	c.10214-741A>G		intron_variant		ENST00000613296.6
ALMS1	NM_015120.4	c.10214-741A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000613296.6	c.10214-741A>G		intron_variant		1	NM_001378454.1	P3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58855 AN: 151988 Hom.: 15889 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.388 AC: 58976 AN: 152106 Hom.: 15948 Cov.: 32 AF XY: 0.381 AC XY: 28298 AN XY: 74346

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.00713

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.334

Alfa AF: 0.249 Hom.: 10033

Bravo AF: 0.416

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	8.6
Dann	Benign	0.68

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: rs6546847; hg19: chr2-73785358;