rs76075180

Positions:

chr1-150553917-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019032.6(ADAMTSL4):c.926G>A(p.Arg309Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,611,512 control chromosomes in the GnomAD database, including 1,002 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 59 hom., cov: 30)

Exomes 𝑓: 0.010 ( 943 hom. )

Consequence

ADAMTSL4
NM_019032.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.189

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001585871).

BP6

Variant 1-150553917-G-A is Benign according to our data. Variant chr1-150553917-G-A is described in ClinVar as [Benign]. Clinvar id is 292524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-150553917-G-A is described in Lovd as [Likely_benign]. Variant chr1-150553917-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	6/19	ENST00000271643.9	NP_061905.2
ADAMTSL4-AS2	XR_001738229.2 linkuse as main transcript	n.210+2037C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL4	ENST00000271643.9 linkuse as main transcript	c.926G>A	p.Arg309Gln	missense_variant	6/19	5	NM_019032.6	ENSP00000271643	P1	Q6UY14-1
ADAMTSL4-AS2	ENST00000442435.3 linkuse as main transcript	n.476+618C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1692

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0690

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0592

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0314

AC:

7572

AN:

240808

Hom.:

595

AF XY:

0.0260

AC XY:

3410

AN XY:

131380

show subpopulations

Gnomad AFR exome

AF:

0.00260

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.000614

Gnomad EAS exome

AF:

0.0519

Gnomad SAS exome

AF:

0.0247

Gnomad FIN exome

AF:

0.000661

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0100

AC:

14656

AN:

1459238

Hom.:

943

Cov.:

AF XY:

0.00981

AC XY:

7120

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.00108

Gnomad4 EAS exome

AF:

0.0963

Gnomad4 SAS exome

AF:

0.0227

Gnomad4 FIN exome

AF:

0.000683

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.00786

GnomAD4 genome

AF:

0.0111

AC:

1689

AN:

152274

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

961

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.0689

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0588

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00336

Hom.:

Bravo

AF:

0.0189

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.0249

AC:

3011

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	This variant is associated with the following publications: (PMID: 20564469) -
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 2, isolated, autosomal recessive

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

Ectopia lentis et pupillae

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.3

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0048

T;.;.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.78

.;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.052

B;.;B;B

Vest4

0.053

MPC

0.14

ClinPred

0.0050

GERP RS

2.3

Varity_R

0.052

gMVP

0.18

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