chr2-73567277-A-G

Variant names:

• chr2-73567277-A-G
• rs10198549
• NM_001378454.1:c.10385-4985A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015120.4(ALMS1):​c.10385-4985A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,062 control chromosomes in the GnomAD database, including 8,607 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 0.30 (8607 hom., cov: 32)
• Consequence: ALMS1 NM_015120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 10 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015120.4. 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.10385-4985A>G		intron	N/A	NP_001365383.1
	ALMS1	NM_015120.4		c.10385-4985A>G		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.10385-4985A>G		intron	N/A	ENSP00000482968.1
	ALMS1	ENST00000484298.5	TSL:1	c.10259-4985A>G		intron	N/A	ENSP00000478155.1
	ALMS1	ENST00000423048.5	TSL:1	n.*804-4985A>G		intron	N/A	ENSP00000399833.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46201 AN: 151944 Hom.: 8570 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.304 AC: 46293 AN: 152062 Hom.: 8607 Cov.: 32 AF XY: 0.298 AC XY: 22152 AN XY: 74320

African (AFR) AF: 0.528 AC: 21882 AN: 41436

American (AMR) AF: 0.258 AC: 3938 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3466

East Asian (EAS) AF: 0.00445 AC: 23 AN: 5164

South Asian (SAS) AF: 0.146 AC: 703 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2349 AN: 10604

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15872 AN: 67978

Other (OTH) AF: 0.280 AC: 592 AN: 2112

Alfa AF: 0.248 Hom.: 2737

Bravo AF: 0.317

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.74
DANN	Benign	0.28
PhyloP100		-1.5
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: rs10198549; hg19: chr2-73794404;