chr1-150553568-G-C

Position:

chr1-150553568-G-C

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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:):

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=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 id is 261079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-150553568-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 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.577G>C	p.Ala193Pro	missense_variant	6/19	ENST00000271643.9	NP_061905.2	Q6UY14-1Q9UFG7B7ZMJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL4	ENST00000271643.9 linkuse as main transcript	c.577G>C	p.Ala193Pro	missense_variant	6/19	5	NM_019032.6	ENSP00000271643.4		Q6UY14-1

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

GnomAD3 exomes

AF:

0.522

AC:

131133

AN:

251424

Hom.:

34885

AF XY:

0.513

AC XY:

69684

AN XY:

135894

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 SAS exome

AF:

0.408

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

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.497

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.643

Gnomad4 NFE exome

AF:

0.529

Gnomad4 OTH exome

AF:

0.517

GnomAD4 genome

AF:

0.542

AC:

82024

AN:

151240

Hom.:

22485

Cov.:

AF XY:

0.545

AC XY:

40269

AN XY:

73830

show subpopulations

Gnomad4 AFR

AF:

0.599

Gnomad4 AMR

AF:

0.476

Gnomad4 ASJ

AF:

0.434

Gnomad4 EAS

AF:

0.551

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.656

Gnomad4 NFE

AF:

0.521

Gnomad4 OTH

AF:

0.530

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

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Ectopia lentis 2, isolated, autosomal recessive

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
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. -

not provided

Benign:2

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

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

0.051

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.035

DANN

Benign

0.67

DEOGEN2

Benign

0.00037

T;.;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.14

.;T;T;T

MetaRNN

Benign

0.0000082

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

1.4

N;N;N;N

REVEL

Benign

0.061

Sift

Benign

0.82

T;T;T;T

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.027

MPC

0.16

ClinPred

0.0029

GERP RS

-4.6

Varity_R

0.048

gMVP

0.25

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