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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019032.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADAMTSL4	NM_019032.6	MANE Select	c.2484G>A	p.Pro828Pro	synonymous	Exon 15 of 19	NP_061905.2
ADAMTSL4	NM_001288608.2		c.2553G>A	p.Pro851Pro	synonymous	Exon 16 of 20	NP_001275537.1
ADAMTSL4	NM_001378596.1		c.2484G>A	p.Pro828Pro	synonymous	Exon 15 of 19	NP_001365525.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.2484G>A	p.Pro828Pro	synonymous	Exon 15 of 19	ENSP00000271643.4
ADAMTSL4	ENST00000369038.6	TSL:1	c.2484G>A	p.Pro828Pro	synonymous	Exon 13 of 17	ENSP00000358034.2
ADAMTSL4	ENST00000369039.9	TSL:5	c.2553G>A	p.Pro851Pro	synonymous	Exon 16 of 20	ENSP00000358035.5

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

21268

42536

63804

85072

106340

<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:

0.854

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.844

Hom.:

34734

Bravo

AF:

0.850

Asia WGS

AF:

0.889

AC:

3091

AN:

3478

EpiCase

AF:

0.836

EpiControl

AF:

0.832

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Ectopia lentis et pupillae (2)

not provided (2)

Ectopia lentis 2, isolated, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over