rs75477151

Positions:

chr1-150554089-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_019032.6(ADAMTSL4):c.1098G>A(p.Gly366=) 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

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 -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL4	NM_019032.6 linkuse as main transcript	c.1098G>A	p.Gly366=	synonymous_variant	6/19	ENST00000271643.9
ADAMTSL4-AS2	XR_001738229.2 linkuse as main transcript	n.210+1865C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL4	ENST00000271643.9 linkuse as main transcript	c.1098G>A	p.Gly366=	synonymous_variant	6/19	5	NM_019032.6	P1	Q6UY14-1
ADAMTSL4-AS2	ENST00000442435.3 linkuse as main transcript	n.476+446C>T		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes

AF:

0.00903

AC:

2121

AN:

234856

Hom.:

AF XY:

0.00773

AC XY:

999

AN XY:

129272

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 SAS exome

AF:

0.00151

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

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0254

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.0467

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.00977

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152252

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

415

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0502

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00951

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00806

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 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	Jan 13, 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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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