rs13008860

chr2-73546892-G-A

Variant summary

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

The NM_001378454.1(ALMS1):c.9908-3375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,034 control chromosomes in the GnomAD database, including 27,083 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 0.56 (27083 hom., cov: 31)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALMS1	NM_001378454.1	c.9908-3375G>A		intron_variant		ENST00000613296.6
ALMS1	NM_015120.4	c.9908-3375G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000613296.6	c.9908-3375G>A		intron_variant		1	NM_001378454.1	P3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84856 AN: 151916 Hom.: 27021 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.559 AC: 84977 AN: 152034 Hom.: 27083 Cov.: 31 AF XY: 0.556 AC XY: 41315 AN XY: 74282

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.521

Alfa AF: 0.427 Hom.: 28870

Bravo AF: 0.581

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.19

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: rs13008860; hg19: chr2-73774019;