2-73546892-G-A

Variant names:

• chr2-73546892-G-A
• rs13008860
• NM_001378454.1:c.9908-3375G>A

Variant summary

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

The NM_001378454.1(ALMS1):​c.9908-3375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,034 control chromosomes in the GnomAD database, including 27,083 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 (27083 hom., cov: 31)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 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.9908-3375G>A		intron	N/A	NP_001365383.1
	ALMS1	NM_015120.4		c.9908-3375G>A		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.9908-3375G>A		intron	N/A	ENSP00000482968.1
	ALMS1	ENST00000484298.5	TSL:1	c.9782-3375G>A		intron	N/A	ENSP00000478155.1
	ALMS1	ENST00000423048.5	TSL:1	n.*327-3375G>A		intron	N/A	ENSP00000399833.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84856 AN: 151916 Hom.: 27021 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.559 AC: 84977 AN: 152034 Hom.: 27083 Cov.: 31 AF XY: 0.556 AC XY: 41315 AN XY: 74282

African (AFR) AF: 0.890 AC: 36951 AN: 41516

American (AMR) AF: 0.490 AC: 7486 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3270 AN: 5160

South Asian (SAS) AF: 0.433 AC: 2082 AN: 4806

European-Finnish (FIN) AF: 0.433 AC: 4565 AN: 10546

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27659 AN: 67952

Other (OTH) AF: 0.521 AC: 1098 AN: 2106

Alfa AF: 0.451 Hom.: 71239

Bravo AF: 0.581

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.19
PhyloP100		-0.61
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: rs13008860; hg19: chr2-73774019;