rs34617744

Variant names:

Your query was ambiguous. Multiple possible variants found:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -17 ACMG points: 0P and 17B. BA1BP4_StrongBP6_StrongBP7

The NM_001378454.1(ALMS1):c.10209T>A (p.Thr3403Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0134 (AC=21,691) in the gnomAD database across 1,614,092 control chromosomes, including 906 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.162. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 124 hom., cov: 32)

Exomes 𝑓: 0.013 ( 782 hom. )

Consequence

ALMS1
NM_001378454.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.44

Publications

3 publications found

Variant links:

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: Unknown, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ALMS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001378454.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BP7

Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1623 — exceeds 5%% threshold (BA1 applied)

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.10209T>A	p.Thr3403Thr	synonymous	Exon 14 of 23	NP_001365383.1	Q8TCU4-1
	ALMS1	NM_015120.4		c.10209T>A	p.Thr3403Thr	synonymous	Exon 14 of 23	NP_055935.4	Q8TCU4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALMS1	ENST00000613296.6	TSL:1 MANE Select	c.10209T>A	p.Thr3403Thr	synonymous	Exon 14 of 23	ENSP00000482968.1	Q8TCU4-1
ALMS1	ENST00000484298.5	TSL:1	c.10083T>A	p.Thr3361Thr	synonymous	Exon 13 of 22	ENSP00000478155.1	A0A087WTU9
ALMS1	ENST00000423048.5	TSL:1	n.*628T>A		3_prime_UTR	Exon 7 of 9	ENSP00000399833.1	H7C1D9

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3333

AN:

152174

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0868

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.0211

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00625

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0320

AC:

7963

AN:

249118

AF XY:

0.0249

show subpopulations

Gnomad AFR exome

AF:

0.0336

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.00269

Gnomad EAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.0179

Gnomad NFE exome

AF:

0.00616

Gnomad OTH exome

AF:

0.0242

GnomAD4 exome

AF:

0.0125

AC:

18343

AN:

1461800

Hom.:

782

Cov.:

AF XY:

0.0116

AC XY:

8422

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0302

AC:

1010

AN:

33480

American (AMR)

AF:

0.165

AC:

7400

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00268

AC:

AN:

26132

East Asian (EAS)

AF:

0.00804

AC:

319

AN:

39678

South Asian (SAS)

AF:

0.00315

AC:

272

AN:

86256

European-Finnish (FIN)

AF:

0.0182

AC:

974

AN:

53408

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00681

AC:

7573

AN:

1111964

Other (OTH)

AF:

0.0116

AC:

698

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

975

1950

2926

3901

4876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0220

AC:

3348

AN:

152292

Hom.:

124

Cov.:

AF XY:

0.0234

AC XY:

1742

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0308

AC:

1282

AN:

41566

American (AMR)

AF:

0.0873

AC:

1335

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00270

AC:

AN:

5186

South Asian (SAS)

AF:

0.00415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0211

AC:

224

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00625

AC:

425

AN:

68012

Other (OTH)

AF:

0.0170

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

156

313

469

626

782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00515

Hom.:

Bravo

AF:

0.0294

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00545

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0148

AC:

1815

AN:

122750

Turkish Variome

AF:

0.00299

AC:

AN:

6692

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.00123

AC:

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.0243

AC:

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Alstrom syndrome (2)

not provided (2)

not specified (2)

Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.4

(source)

DANN

Benign

0.57

PhyloP100

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over