chr2-73513298-G-A

Position:

• chr2-73513298-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.9540-6477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,766 control chromosomes in the GnomAD database, including 26,952 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 0.56 (26952 hom., cov: 30)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALMS1	NM_001378454.1	c.9540-6477G>A		intron_variant		ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4	c.9540-6477G>A		intron_variant			NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6	c.9540-6477G>A		intron_variant		1	NM_001378454.1	ENSP00000482968	P3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84457 AN: 151648 Hom.: 26892 Cov.: 30

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.557 AC: 84576 AN: 151766 Hom.: 26952 Cov.: 30 AF XY: 0.555 AC XY: 41139 AN XY: 74132

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.518

Alfa AF: 0.484 Hom.: 3443

Bravo AF: 0.580

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.56

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: rs7598660; hg19: chr2-73740425;