1-150554089-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_019032.6(ADAMTSL4):c.1098G>A(p.Gly366Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,601,516 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 73 hom. )

Consequence

ADAMTSL4
NM_019032.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0850

Publications

5 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-150554089-G-A is Benign according to our data. Variant chr1-150554089-G-A is described in ClinVar as [Benign]. Clinvar id is 261075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.085 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00488 (743/152252) while in subpopulation EAS AF = 0.0502 (259/5164). AF 95% confidence interval is 0.0451. There are 8 homozygotes in GnomAd4. There are 415 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6 link	c.1098G>A	p.Gly366Gly	synonymous_variant	Exon 6 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.1098G>A	p.Gly366Gly	synonymous_variant	Exon 6 of 19	5	NM_019032.6	ENSP00000271643.4		Q6UY14-1

Frequencies

GnomAD3 genomes

AF:

0.00490

AC:

745

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0500

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00951

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00814

GnomAD2 exomes

AF:

0.00903

AC:

2121

AN:

234856

AF XY:

0.00773

show subpopulations

Gnomad AFR exome

AF:

0.000354

Gnomad AMR exome

AF:

0.0260

Gnomad ASJ exome

AF:

0.000304

Gnomad EAS exome

AF:

0.0535

Gnomad FIN exome

AF:

0.00885

Gnomad NFE exome

AF:

0.000679

Gnomad OTH exome

AF:

0.00559

GnomAD4 exome

AF:

0.00279

AC:

4044

AN:

1449264

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

1914

AN XY:

721324

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33476

American (AMR)

AF:

0.0254

AC:

1135

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.0467

AC:

1854

AN:

39700

South Asian (SAS)

AF:

0.00176

AC:

152

AN:

86248

European-Finnish (FIN)

AF:

0.00977

AC:

401

AN:

41034

Middle Eastern (MID)

AF:

0.000874

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000203

AC:

226

AN:

1111924

Other (OTH)

AF:

0.00416

AC:

251

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

271

543

814

1086

1357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152252

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

415

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.000578

AC:

AN:

41552

American (AMR)

AF:

0.0184

AC:

282

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0502

AC:

259

AN:

5164

South Asian (SAS)

AF:

0.00373

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00951

AC:

101

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68000

Other (OTH)

AF:

0.00806

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.00654

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ectopia lentis 2, isolated, autosomal recessive

Benign:2

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. -

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ectopia lentis et pupillae

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.085

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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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1-150554089-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over