dbSNP rs6546857: ALMS1:n.*2996+1146A>G (chr2-73610828-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000651434.1(ALMS1):n.*2996+1146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,188 control chromosomes in the GnomAD database, including 9,175 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 0.31 ( 9172 hom., cov: 32)

Exomes 𝑓: 0.60 ( 3 hom. )

Consequence

ALMS1
ENST00000651434.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

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

ALMS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000651434.1 link	n.*2996+1146A>G		intron_variant	Intron 15 of 16			ENSP00000498259.1
ALMS1	ENST00000490821.1 link	n.*35A>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47518

AN:

152050

Hom.:

9138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.00462

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.290

GnomAD4 exome

AF:

0.600

AC:

AN:

Hom.:

Cov.:

AF XY:

0.563

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.556

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.313

AC:

47607

AN:

152168

Hom.:

9172

Cov.:

AF XY:

0.307

AC XY:

22808

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.543

AC:

22529

AN:

41484

American (AMR)

AF:

0.263

AC:

4028

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

512

AN:

3472

East Asian (EAS)

AF:

0.00463

AC:

AN:

5184

South Asian (SAS)

AF:

0.146

AC:

707

AN:

4826

European-Finnish (FIN)

AF:

0.234

AC:

2478

AN:

10602

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16410

AN:

67994

Other (OTH)

AF:

0.287

AC:

606

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1539

3078

4616

6155

7694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.269

Hom.:

10533

Bravo

AF:

0.325

Asia WGS

AF:

0.105

AC:

365

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over