rs11126402

chr2-73549455-G-C

Variant summary

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

The NM_001378454.1(ALMS1):c.9908-812G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,856 control chromosomes in the GnomAD database, including 18,705 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 0.47 (18705 hom., cov: 31)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALMS1	NM_001378454.1	c.9908-812G>C		intron_variant		ENST00000613296.6
ALMS1	NM_015120.4	c.9908-812G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALMS1	ENST00000613296.6	c.9908-812G>C		intron_variant		1	NM_001378454.1	P3

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71415 AN: 151738 Hom.: 18655 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.471 AC: 71531 AN: 151856 Hom.: 18705 Cov.: 31 AF XY: 0.466 AC XY: 34592 AN XY: 74200

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.440

Alfa AF: 0.430 Hom.: 1930

Bravo AF: 0.488

Asia WGS AF: 0.304 AC: 1056 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.32
Dann	Benign	0.37

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: rs11126402; hg19: chr2-73776582;