rs41317515

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019032.6(ADAMTSL4):c.577G>C(p.Ala193Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,613,072 control chromosomes in the GnomAD database, including 225,534 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22485 hom., cov: 28)

Exomes 𝑓: 0.52 ( 203049 hom. )

Consequence

ADAMTSL4
NM_019032.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.17

Publications

36 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 links:

ADAMTSL4-AS2 (HGNC:40895): (ADAMTSL4 antisense RNA 2)

ADAMTSL4-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.249086E-6).

BP6

Variant 1-150553568-G-C is Benign according to our data. Variant chr1-150553568-G-C is described in ClinVar as Benign. ClinVar VariationId is 261079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 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	UniProt
ADAMTSL4	NM_019032.6	MANE Select	c.577G>C	p.Ala193Pro	missense	Exon 6 of 19	NP_061905.2
ADAMTSL4	NM_001288608.2		c.577G>C	p.Ala193Pro	missense	Exon 6 of 20	NP_001275537.1	Q6UY14-3
ADAMTSL4	NM_001378596.1		c.577G>C	p.Ala193Pro	missense	Exon 6 of 19	NP_001365525.1	Q6UY14-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.577G>C	p.Ala193Pro	missense	Exon 6 of 19	ENSP00000271643.4	Q6UY14-1
ADAMTSL4	ENST00000369038.6	TSL:1	c.577G>C	p.Ala193Pro	missense	Exon 4 of 17	ENSP00000358034.2	Q6UY14-1
ADAMTSL4	ENST00000369039.9	TSL:5	c.577G>C	p.Ala193Pro	missense	Exon 6 of 20	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

81953

AN:

151122

Hom.:

22461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.552

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.391

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.535

GnomAD2 exomes

AF:

0.522

AC:

131133

AN:

251424

AF XY:

0.513

show subpopulations

Gnomad AFR exome

AF:

0.598

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.650

Gnomad NFE exome

AF:

0.526

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.525

AC:

767392

AN:

1461832

Hom.:

203049

Cov.:

AF XY:

0.519

AC XY:

377632

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.598

AC:

20035

AN:

33480

American (AMR)

AF:

0.497

AC:

22215

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

11311

AN:

26134

East Asian (EAS)

AF:

0.560

AC:

22216

AN:

39698

South Asian (SAS)

AF:

0.408

AC:

35187

AN:

86258

European-Finnish (FIN)

AF:

0.643

AC:

34330

AN:

53420

Middle Eastern (MID)

AF:

0.501

AC:

2888

AN:

5768

European-Non Finnish (NFE)

AF:

0.529

AC:

588004

AN:

1111962

Other (OTH)

AF:

0.517

AC:

31206

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

25948

51896

77845

103793

129741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16864

33728

50592

67456

84320

<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:

0.542

AC:

82024

AN:

151240

Hom.:

22485

Cov.:

AF XY:

0.545

AC XY:

40269

AN XY:

73830

show subpopulations

African (AFR)

AF:

0.599

AC:

24641

AN:

41156

American (AMR)

AF:

0.476

AC:

7241

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

1504

AN:

3464

East Asian (EAS)

AF:

0.551

AC:

2801

AN:

5082

South Asian (SAS)

AF:

0.417

AC:

1996

AN:

4784

European-Finnish (FIN)

AF:

0.656

AC:

6869

AN:

10466

Middle Eastern (MID)

AF:

0.400

AC:

116

AN:

290

European-Non Finnish (NFE)

AF:

0.521

AC:

35280

AN:

67774

Other (OTH)

AF:

0.530

AC:

1115

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1836

3671

5507

7342

9178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.513

Hom.:

6545

Bravo

AF:

0.536

TwinsUK

AF:

0.536

AC:

1989

ALSPAC

AF:

0.530

AC:

2043

ESP6500AA

AF:

0.590

AC:

2600

ESP6500EA

AF:

0.525

AC:

4515

ExAC

AF:

0.523

AC:

63487

Asia WGS

AF:

0.516

AC:

1791

AN:

3478

EpiCase

AF:

0.505

EpiControl

AF:

0.512

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ectopia lentis 2, isolated, autosomal recessive (2)

not provided (2)

not specified (2)

Ectopia lentis et pupillae (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.035

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.00037

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0000083

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PhyloP100

-1.2

PrimateAI

Benign

0.30

PROVEAN

Benign

1.4

REVEL

Benign

0.061

Sift

Benign

0.82

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.027

MPC

0.16

ClinPred

0.0029

GERP RS

-4.6

Varity_R

0.048

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over