dbSNP rs890309: ADAMTSL3:c.189+110G>A (chr15-83704618-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.189+110G>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 1,433,164 control chromosomes in the GnomAD database, including 44,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3965 hom., cov: 33)

Exomes 𝑓: 0.24 ( 40395 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0200

Publications

2 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=-0.87).

BP6

Variant 15-83704618-G-A is Benign according to our data. Variant chr15-83704618-G-A is described in ClinVar as Benign. ClinVar VariationId is 1279078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.333 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.189+110G>A		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.189+110G>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.189+110G>A	intron	N/A	ENSP00000286744.5	P82987-1
ADAMTSL3	ENST00000567476.1	TSL:1	c.189+110G>A	intron	N/A	ENSP00000456313.1	P82987-2
ADAMTSL3	ENST00000963409.1		c.189+110G>A	intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30332

AN:

152036

Hom.:

3960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0481

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.0722

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.244

AC:

312291

AN:

1281010

Hom.:

40395

AF XY:

0.242

AC XY:

153906

AN XY:

635620

show subpopulations

African (AFR)

AF:

0.0392

AC:

1123

AN:

28642

American (AMR)

AF:

0.361

AC:

12151

AN:

33700

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

6964

AN:

20830

East Asian (EAS)

AF:

0.0781

AC:

2997

AN:

38358

South Asian (SAS)

AF:

0.170

AC:

11770

AN:

69310

European-Finnish (FIN)

AF:

0.198

AC:

9900

AN:

50032

Middle Eastern (MID)

AF:

0.382

AC:

1564

AN:

4094

European-Non Finnish (NFE)

AF:

0.258

AC:

253186

AN:

982420

Other (OTH)

AF:

0.236

AC:

12636

AN:

53624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

10903

21806

32709

43612

54515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8260

16520

24780

33040

41300

<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:

0.199

AC:

30339

AN:

152154

Hom.:

3965

Cov.:

AF XY:

0.198

AC XY:

14705

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0479

AC:

1991

AN:

41536

American (AMR)

AF:

0.340

AC:

5202

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1130

AN:

3470

East Asian (EAS)

AF:

0.0724

AC:

375

AN:

5180

South Asian (SAS)

AF:

0.157

AC:

761

AN:

4832

European-Finnish (FIN)

AF:

0.203

AC:

2145

AN:

10558

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17829

AN:

67990

Other (OTH)

AF:

0.247

AC:

519

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1208

2416

3624

4832

6040

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:

0.234

Hom.:

888

Bravo

AF:

0.206

Asia WGS

AF:

0.127

AC:

442

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

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.41

PhyloP100

-0.020

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