rs369656698

Variant names:

• chr2-73452059-C-T
• rs369656698
• NM_001378454.1:c.5532C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-73452059-C-T
• chr2-73452059-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_001378454.1(ALMS1):​c.5532C>T​(p.Asn1844Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ALMS1 NM_001378454.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: -0.169
• Publications: 0 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 -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-73452059-C-T is Benign according to our data. Variant chr2-73452059-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 556360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.169 with no splicing effect.

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.5532C>T	p.Asn1844Asn	synonymous	Exon 8 of 23	NP_001365383.1	Q8TCU4-1
	ALMS1	NM_015120.4		c.5532C>T	p.Asn1844Asn	synonymous	Exon 8 of 23	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.5532C>T	p.Asn1844Asn	synonymous	Exon 8 of 23	ENSP00000482968.1	Q8TCU4-1
	ALMS1	ENST00000484298.5	TSL:1	c.5406C>T	p.Asn1802Asn	synonymous	Exon 7 of 22	ENSP00000478155.1	A0A087WTU9
	ALMS1	ENST00000423048.5	TSL:1	n.363C>T		non_coding_transcript_exon	Exon 1 of 9	ENSP00000399833.1	H7C1D9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 249094 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461820 Hom.: 0 Cov.: 38 AF XY: 0.0000151 AC XY: 11 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000895 AC: 4 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111974

Other (OTH) AF: 0.0000331 AC: 2 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	1	Alstrom syndrome (2)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.42
PhyloP100		-0.17
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs369656698; hg19: chr2-73679186;