2-73525241-G-A

Position:

• chr2-73525241-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.9781+5225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,074 control chromosomes in the GnomAD database, including 6,111 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 0.27 (6111 hom., cov: 32)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALMS1	NM_001378454.1	c.9781+5225G>A		intron_variant		ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4	c.9781+5225G>A		intron_variant			NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6	c.9781+5225G>A		intron_variant		1	NM_001378454.1	ENSP00000482968	P3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41489 AN: 151956 Hom.: 6105 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.273 AC: 41522 AN: 152074 Hom.: 6111 Cov.: 32 AF XY: 0.268 AC XY: 19888 AN XY: 74314

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.00462

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.264

Alfa AF: 0.268 Hom.: 782

Bravo AF: 0.279

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.7
DANN	Benign	0.70

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: rs10469966; hg19: chr2-73752368;