rs1320374

Variant names:

• chr2-73601183-T-C
• rs1320374
• NM_001378454.1:c.11873-12T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-73601183-T-C
• chr2-73601183-T-A
• chr2-73601183-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378454.1(ALMS1):​c.11873-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,613,652 control chromosomes in the GnomAD database, including 318,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23968 hom., cov: 33)
  • Exomes 𝑓: 0.63 (294586 hom.)
• Consequence: ALMS1 NM_001378454.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.33
• Publications: 18 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, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-73601183-T-C is Benign according to our data. Variant chr2-73601183-T-C is described in ClinVar as Benign. ClinVar VariationId is 383770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	NM_001378454.1	MANE Select	c.11873-12T>C		intron	N/A	NP_001365383.1	Q8TCU4-1
	ALMS1	NM_015120.4		c.11873-12T>C		intron	N/A	NP_055935.4	Q8TCU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.11873-12T>C		intron	N/A	ENSP00000482968.1	Q8TCU4-1
	ALMS1	ENST00000484298.5	TSL:1	c.11747-12T>C		intron	N/A	ENSP00000478155.1	A0A087WTU9
	ALMS1	ENST00000684548.1		c.11492-12T>C		intron	N/A	ENSP00000507421.1	A0A804HJA5

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80501 AN: 152014 Hom.: 23970 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.567

GnomAD2 exomes AF: 0.635 AC: 158858 AN: 250274 AF XY: 0.639

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.722

Gnomad ASJ exome AF: 0.683

Gnomad EAS exome AF: 0.757

Gnomad FIN exome AF: 0.627

Gnomad NFE exome AF: 0.632

Gnomad OTH exome AF: 0.650

GnomAD4 exome AF: 0.630 AC: 921376 AN: 1461518 Hom.: 294586 Cov.: 64 AF XY: 0.632 AC XY: 459391 AN XY: 727062

African (AFR) AF: 0.210 AC: 7043 AN: 33474

American (AMR) AF: 0.710 AC: 31751 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 17837 AN: 26136

East Asian (EAS) AF: 0.734 AC: 29134 AN: 39698

South Asian (SAS) AF: 0.667 AC: 57398 AN: 86074

European-Finnish (FIN) AF: 0.632 AC: 33757 AN: 53414

Middle Eastern (MID) AF: 0.617 AC: 3557 AN: 5766

European-Non Finnish (NFE) AF: 0.632 AC: 702732 AN: 1111856

Other (OTH) AF: 0.632 AC: 38167 AN: 60382

GnomAD4 genome AF: 0.529 AC: 80512 AN: 152134 Hom.: 23968 Cov.: 33 AF XY: 0.536 AC XY: 39893 AN XY: 74362

African (AFR) AF: 0.231 AC: 9575 AN: 41508

American (AMR) AF: 0.646 AC: 9876 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2314 AN: 3470

East Asian (EAS) AF: 0.745 AC: 3851 AN: 5168

South Asian (SAS) AF: 0.677 AC: 3267 AN: 4828

European-Finnish (FIN) AF: 0.629 AC: 6656 AN: 10574

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42968 AN: 67976

Other (OTH) AF: 0.567 AC: 1200 AN: 2116

Alfa AF: 0.592 Hom.: 9131

Bravo AF: 0.517

Asia WGS AF: 0.695 AC: 2418 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Alstrom syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.44
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1320374; hg19: chr2-73828310; COSMIC: COSV52503032; COSMIC: COSV52503032;