rs11126402

Variant names:

• chr2-73549455-G-C
• rs11126402
• NM_001378454.1:c.9908-812G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ALMS1 Gene-Disease associations (from GenCC):

• Alstrom syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378454.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	NM_001378454.1	MANE Select	c.9908-812G>C		intron	N/A	NP_001365383.1
	ALMS1	NM_015120.4		c.9908-812G>C		intron	N/A	NP_055935.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.9908-812G>C		intron	N/A	ENSP00000482968.1
	ALMS1	ENST00000484298.5	TSL:1	c.9782-812G>C		intron	N/A	ENSP00000478155.1
	ALMS1	ENST00000423048.5	TSL:1	n.*327-812G>C		intron	N/A	ENSP00000399833.1

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

African (AFR) AF: 0.719 AC: 29778 AN: 41430

American (AMR) AF: 0.437 AC: 6656 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1322 AN: 3464

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5168

South Asian (SAS) AF: 0.331 AC: 1589 AN: 4802

European-Finnish (FIN) AF: 0.393 AC: 4134 AN: 10516

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25442 AN: 67920

Other (OTH) AF: 0.440 AC: 925 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.37
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11126402; hg19: chr2-73776582;