rs10749657

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019032.6(ADAMTSL4):c.2484G>A(p.Pro828Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,613,870 control chromosomes in the GnomAD database, including 601,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55558 hom., cov: 32)

Exomes 𝑓: 0.86 ( 546343 hom. )

Consequence

ADAMTSL4
NM_019032.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.85

Publications

16 publications found

Variant links:

Genes affected

ADAMTSL4 (HGNC:19706): (ADAMTS like 4) This gene is a member of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-like gene family and encodes a protein with seven thrombospondin type 1 repeats. The thrombospondin type 1 repeat domain is found in many proteins with diverse biological functions including cellular adhesion, angiogenesis, and patterning of the developing nervous system. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Sep 2014]

ADAMTSL4 Gene-Disease associations (from GenCC):

ectopia lentis 2, isolated, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
ectopia lentis et pupillae
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
isolated ectopia lentis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADAMTSL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-150558574-G-A is Benign according to our data. Variant chr1-150558574-G-A is described in ClinVar as [Benign]. Clinvar id is 261077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6 link	c.2484G>A	p.Pro828Pro	synonymous_variant	Exon 15 of 19	ENST00000271643.9	NP_061905.2	Q6UY14-1Q9UFG7B7ZMJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL4	ENST00000271643.9 link	c.2484G>A	p.Pro828Pro	synonymous_variant	Exon 15 of 19	5	NM_019032.6	ENSP00000271643.4		Q6UY14-1

Frequencies

GnomAD3 genomes

AF:

0.854

AC:

129867

AN:

152062

Hom.:

55511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.841

Gnomad AMI

AF:

0.798

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.910

Gnomad FIN

AF:

0.875

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.851

Gnomad OTH

AF:

0.832

GnomAD2 exomes

AF:

0.870

AC:

218661

AN:

251226

AF XY:

0.871

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.885

Gnomad ASJ exome

AF:

0.816

Gnomad EAS exome

AF:

0.977

Gnomad FIN exome

AF:

0.880

Gnomad NFE exome

AF:

0.848

Gnomad OTH exome

AF:

0.853

GnomAD4 exome

AF:

0.864

AC:

1262936

AN:

1461690

Hom.:

546343

Cov.:

AF XY:

0.864

AC XY:

628598

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.835

AC:

27955

AN:

33480

American (AMR)

AF:

0.880

AC:

39362

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.819

AC:

21412

AN:

26134

East Asian (EAS)

AF:

0.966

AC:

38368

AN:

39700

South Asian (SAS)

AF:

0.901

AC:

77701

AN:

86258

European-Finnish (FIN)

AF:

0.879

AC:

46768

AN:

53230

Middle Eastern (MID)

AF:

0.788

AC:

4546

AN:

5768

European-Non Finnish (NFE)

AF:

0.859

AC:

954868

AN:

1112004

Other (OTH)

AF:

0.860

AC:

51956

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

12469

24937

37406

49874

62343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.854

AC:

129972

AN:

152180

Hom.:

55558

Cov.:

AF XY:

0.857

AC XY:

63755

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.841

AC:

34896

AN:

41510

American (AMR)

AF:

0.844

AC:

12899

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

2843

AN:

3468

East Asian (EAS)

AF:

0.979

AC:

5068

AN:

5176

South Asian (SAS)

AF:

0.912

AC:

4404

AN:

4830

European-Finnish (FIN)

AF:

0.875

AC:

9280

AN:

10600

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.851

AC:

57877

AN:

68002

Other (OTH)

AF:

0.830

AC:

1753

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

993

1986

2980

3973

4966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.844

Hom.:

34734

Bravo

AF:

0.850

Asia WGS

AF:

0.889

AC:

3091

AN:

3478

EpiCase

AF:

0.836

EpiControl

AF:

0.832

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 19, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Ectopia lentis et pupillae

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ectopia lentis 2, isolated, autosomal recessive

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.13

(source)

DANN

Benign

0.87

PhyloP100

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

rs10749657

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over