chr1-150558532-T-C

Variant names:

Variant summary

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

The NM_019032.6(ADAMTSL4):c.2442T>C(p.Asn814Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,613,790 control chromosomes in the GnomAD database, including 703,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58608 hom., cov: 33)

Exomes 𝑓: 0.94 ( 644548 hom. )

Consequence

ADAMTSL4
NM_019032.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.94

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=-0.68).

BP6

Variant 1-150558532-T-C is Benign according to our data. Variant chr1-150558532-T-C is described in ClinVar as [Benign]. Clinvar id is 261076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-150558532-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6 link	c.2442T>C	p.Asn814Asn	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.2442T>C	p.Asn814Asn	synonymous_variant	Exon 15 of 19	5	NM_019032.6	ENSP00000271643.4		Q6UY14-1

Frequencies

GnomAD3 genomes

AF:

0.871

AC:

132483

AN:

152080

Hom.:

58597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.917

Gnomad AMR

AF:

0.893

Gnomad ASJ

AF:

0.925

Gnomad EAS

AF:

0.855

Gnomad SAS

AF:

0.867

Gnomad FIN

AF:

0.980

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.950

Gnomad OTH

AF:

0.872

GnomAD3 exomes

AF:

0.911

AC:

228846

AN:

251148

Hom.:

104870

AF XY:

0.914

AC XY:

124232

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.691

Gnomad AMR exome

AF:

0.908

Gnomad ASJ exome

AF:

0.923

Gnomad EAS exome

AF:

0.847

Gnomad SAS exome

AF:

0.877

Gnomad FIN exome

AF:

0.980

Gnomad NFE exome

AF:

0.949

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.938

AC:

1370865

AN:

1461592

Hom.:

644548

Cov.:

100

AF XY:

0.937

AC XY:

681177

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.695

Gnomad4 AMR exome

AF:

0.907

Gnomad4 ASJ exome

AF:

0.925

Gnomad4 EAS exome

AF:

0.891

Gnomad4 SAS exome

AF:

0.880

Gnomad4 FIN exome

AF:

0.978

Gnomad4 NFE exome

AF:

0.952

Gnomad4 OTH exome

AF:

0.919

GnomAD4 genome

AF:

0.871

AC:

132528

AN:

152198

Hom.:

58608

Cov.:

AF XY:

0.872

AC XY:

64860

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.893

Gnomad4 ASJ

AF:

0.925

Gnomad4 EAS

AF:

0.856

Gnomad4 SAS

AF:

0.868

Gnomad4 FIN

AF:

0.980

Gnomad4 NFE

AF:

0.950

Gnomad4 OTH

AF:

0.873

Alfa

AF:

0.933

Hom.:

89759

Bravo

AF:

0.857

Asia WGS

AF:

0.846

AC:

2942

AN:

3478

EpiCase

AF:

0.946

EpiControl

AF:

0.947

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ectopia lentis et pupillae

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Ectopia lentis 2, isolated, autosomal recessive

Benign:1

Jan 13, 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

-0.68

CADD

Benign

0.50

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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