dbSNP rs6749680: ALMS1-IT1:n.1348G>A (chr2-73458725-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000441587.3(ALMS1-IT1):n.1348G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,178 control chromosomes in the GnomAD database, including 21,445 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 0.50 ( 21421 hom., cov: 32)

Exomes 𝑓: 0.58 ( 24 hom. )

Consequence

ALMS1-IT1
ENST00000441587.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Publications

12 publications found

Variant links:

Genes affected

ALMS1-IT1 (HGNC:41305): (ALMS1 intronic transcript 1)

ALMS1-IT1 links:

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:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALMS1	NM_001378454.1 link	c.7674+3430G>A	intron_variant	Intron 9 of 22	ENST00000613296.6	NP_001365383.1
ALMS1-IT1	NR_046762.1 link	n.1009G>A	non_coding_transcript_exon_variant	Exon 2 of 2
ALMS1	NM_015120.4 link	c.7674+3430G>A	intron_variant	Intron 9 of 22		NP_055935.4	Q8TCU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1	ENST00000613296.6 link	c.7674+3430G>A		intron_variant	Intron 9 of 22	1	NM_001378454.1	ENSP00000482968.1		Q8TCU4-1

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75275

AN:

151928

Hom.:

21427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.529

GnomAD4 exome

AF:

0.576

AC:

AN:

132

Hom.:

Cov.:

AF XY:

0.556

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.532

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.583

AC:

AN:

Other (OTH)

AF:

0.786

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.495

AC:

75271

AN:

152046

Hom.:

21421

Cov.:

AF XY:

0.502

AC XY:

37314

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.192

AC:

7981

AN:

41476

American (AMR)

AF:

0.544

AC:

8317

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

2087

AN:

3472

East Asian (EAS)

AF:

0.769

AC:

3977

AN:

5170

South Asian (SAS)

AF:

0.661

AC:

3184

AN:

4820

European-Finnish (FIN)

AF:

0.606

AC:

6399

AN:

10554

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.610

AC:

41423

AN:

67950

Other (OTH)

AF:

0.529

AC:

1119

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1718

3435

5153

6870

8588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.580

Hom.:

47101

Bravo

AF:

0.475

Asia WGS

AF:

0.689

AC:

2395

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.3

(source)

DANN

Benign

0.81

PhyloP100

0.034

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

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