rs10749657

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019032.6(ADAMTSL4):c.2484G>A(p.Pro828=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr1-150558574-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
ADAMTSL4	NM_019032.6 linkuse as main transcript	c.2484G>A	p.Pro828=	synonymous_variant	15/19	ENST00000271643.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL4	ENST00000271643.9 linkuse as main transcript	c.2484G>A	p.Pro828=	synonymous_variant	15/19	5	NM_019032.6	P1	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

GnomAD3 exomes

AF:

0.870

AC:

218661

AN:

251226

Hom.:

95441

AF XY:

0.871

AC XY:

118309

AN XY:

135864

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 SAS exome

AF:

0.902

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

Gnomad4 AFR exome

AF:

0.835

Gnomad4 AMR exome

AF:

0.880

Gnomad4 ASJ exome

AF:

0.819

Gnomad4 EAS exome

AF:

0.966

Gnomad4 SAS exome

AF:

0.901

Gnomad4 FIN exome

AF:

0.879

Gnomad4 NFE exome

AF:

0.859

Gnomad4 OTH exome

AF:

0.860

GnomAD4 genome

AF:

0.854

AC:

129972

AN:

152180

Hom.:

55558

Cov.:

AF XY:

0.857

AC XY:

63755

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.841

Gnomad4 AMR

AF:

0.844

Gnomad4 ASJ

AF:

0.820

Gnomad4 EAS

AF:

0.979

Gnomad4 SAS

AF:

0.912

Gnomad4 FIN

AF:

0.875

Gnomad4 NFE

AF:

0.851

Gnomad4 OTH

AF:

0.830

Alfa

AF:

0.846

Hom.:

29682

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2017	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ectopia lentis et pupillae

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Ectopia lentis 2, isolated, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over