rs10198549

Variant names:

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

Variant summary

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

The NM_001378454.1(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_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1	c.10385-4985A>G		intron_variant	Intron 15 of 22	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4	c.10385-4985A>G		intron_variant	Intron 15 of 22		NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6	c.10385-4985A>G		intron_variant	Intron 15 of 22	1	NM_001378454.1	ENSP00000482968.1

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

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.00445

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.280

Alfa AF: 0.246 Hom.: 2402

Bravo AF: 0.317

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.74
DANN	Benign	0.28

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: rs10198549; hg19: chr2-73794404;