dbSNP rs2730080: ADAMTSL3:c.-33-40G>A (chr15-83655689-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207517.3(ADAMTSL3):c.-33-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,455,024 control chromosomes in the GnomAD database, including 45,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4067 hom., cov: 32)

Exomes 𝑓: 0.24 ( 41625 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0170

Publications

4 publications found

Variant links:

Genes affected

ADAMTSL3 (HGNC:14633): (ADAMTS like 3) Predicted to be involved in extracellular matrix organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ADAMTSL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-83655689-G-A is Benign according to our data. Variant chr15-83655689-G-A is described in ClinVar as Benign. ClinVar VariationId is 1258788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207517.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	NM_207517.3	MANE Select	c.-33-40G>A		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.-33-40G>A		intron	N/A	NP_001288039.1	P82987-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAMTSL3	ENST00000286744.10	TSL:1 MANE Select	c.-33-40G>A	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.-33-40G>A	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.-33-40G>A	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30763

AN:

152056

Hom.:

4062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0497

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.0677

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.243

AC:

317232

AN:

1302850

Hom.:

41625

Cov.:

AF XY:

0.241

AC XY:

157837

AN XY:

653948

show subpopulations

African (AFR)

AF:

0.0397

AC:

1204

AN:

30310

American (AMR)

AF:

0.384

AC:

16199

AN:

42218

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

8535

AN:

24488

East Asian (EAS)

AF:

0.0775

AC:

2974

AN:

38368

South Asian (SAS)

AF:

0.158

AC:

12761

AN:

80554

European-Finnish (FIN)

AF:

0.233

AC:

12194

AN:

52444

Middle Eastern (MID)

AF:

0.357

AC:

1945

AN:

5446

European-Non Finnish (NFE)

AF:

0.255

AC:

248604

AN:

973912

Other (OTH)

AF:

0.233

AC:

12816

AN:

55110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

11122

22244

33367

44489

55611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7796

15592

23388

31184

38980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.202

AC:

30769

AN:

152174

Hom.:

4067

Cov.:

AF XY:

0.201

AC XY:

14952

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0495

AC:

2057

AN:

41548

American (AMR)

AF:

0.342

AC:

5229

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1172

AN:

3470

East Asian (EAS)

AF:

0.0681

AC:

352

AN:

5172

South Asian (SAS)

AF:

0.134

AC:

647

AN:

4826

European-Finnish (FIN)

AF:

0.239

AC:

2530

AN:

10596

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17903

AN:

67972

Other (OTH)

AF:

0.245

AC:

516

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1155

2310

3464

4619

5774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.224

Hom.:

720

Bravo

AF:

0.207

Asia WGS

AF:

0.110

AC:

383

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.2

(source)

DANN

Benign

0.60

PhyloP100

0.017

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over