2-73604587-T-G

Variant names:

• chr2-73604587-T-G
• rs17349853
• NM_001378454.1:c.12362+1283T>G

Variant summary

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

The NM_001378454.1(ALMS1):​c.12362+1283T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,248 control chromosomes in the GnomAD database, including 313 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 0.052 (313 hom., cov: 32)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1	c.12362+1283T>G		intron_variant	Intron 21 of 22	ENST00000613296.6	NP_001365383.1
ALMS1	NM_015120.4	c.12362+1283T>G		intron_variant	Intron 21 of 22		NP_055935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6	c.12362+1283T>G		intron_variant	Intron 21 of 22	1	NM_001378454.1	ENSP00000482968.1

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7852 AN: 152130 Hom.: 313 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0516 AC: 7854 AN: 152248 Hom.: 313 Cov.: 32 AF XY: 0.0509 AC XY: 3787 AN XY: 74448

African (AFR) AF: 0.0135 AC: 561 AN: 41548

American (AMR) AF: 0.0328 AC: 501 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3466

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4824

European-Finnish (FIN) AF: 0.106 AC: 1123 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0795 AC: 5408 AN: 68006

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0550 Hom.: 323

Bravo AF: 0.0438

Asia WGS AF: 0.00953 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.76
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17349853; hg19: chr2-73831714;