dbSNP rs11182085: ADAMTS20:c.1760+27T>C (chr12-43453880-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_025003.5(ADAMTS20):c.1760+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 1,565,280 control chromosomes in the GnomAD database, including 9,713 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.086 ( 1005 hom., cov: 32)

Exomes 𝑓: 0.091 ( 8708 hom. )

Consequence

ADAMTS20
NM_025003.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Publications

11 publications found

Variant links:

Genes affected

ADAMTS20 (HGNC:17178): (ADAM metallopeptidase with thrombospondin type 1 motif 20) The protein encoded by this gene is a member of the ADAMTS family of zinc-dependent proteases. The encoded protein has a signal peptide that is cleaved to release the mature peptide, which is secreted and found in the extracellular matrix. This protein may be involved in tissue remodeling. [provided by RefSeq, Sep 2011]

ADAMTS20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025003.5. 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
	ADAMTS20	NM_025003.5	MANE Select	c.1760+27T>C		intron	N/A	NP_079279.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAMTS20	ENST00000389420.8	TSL:1 MANE Select	c.1760+27T>C	intron	N/A	ENSP00000374071.3	P59510-3
ADAMTS20	ENST00000935091.1		c.1763+27T>C	intron	N/A	ENSP00000605150.1
ADAMTS20	ENST00000553158.5	TSL:5	c.1760+27T>C	intron	N/A	ENSP00000448341.1	G3V1X8

Frequencies

GnomAD3 genomes

AF:

0.0860

AC:

13080

AN:

152036

Hom.:

1001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0548

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.0739

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0740

Gnomad OTH

AF:

0.0861

GnomAD2 exomes

AF:

0.119

AC:

21628

AN:

181322

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.0440

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.0574

Gnomad EAS exome

AF:

0.490

Gnomad FIN exome

AF:

0.0764

Gnomad NFE exome

AF:

0.0762

Gnomad OTH exome

AF:

0.0969

GnomAD4 exome

AF:

0.0910

AC:

128656

AN:

1413126

Hom.:

8708

Cov.:

AF XY:

0.0903

AC XY:

63071

AN XY:

698580

show subpopulations

African (AFR)

AF:

0.0415

AC:

1338

AN:

32248

American (AMR)

AF:

0.166

AC:

6185

AN:

37180

Ashkenazi Jewish (ASJ)

AF:

0.0572

AC:

1451

AN:

25348

East Asian (EAS)

AF:

0.430

AC:

16069

AN:

37332

South Asian (SAS)

AF:

0.0833

AC:

6709

AN:

80548

European-Finnish (FIN)

AF:

0.0750

AC:

3780

AN:

50432

Middle Eastern (MID)

AF:

0.0310

AC:

177

AN:

5704

European-Non Finnish (NFE)

AF:

0.0802

AC:

87108

AN:

1085744

Other (OTH)

AF:

0.0997

AC:

5839

AN:

58590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

5495

10990

16486

21981

27476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3510

7020

10530

14040

17550

<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:

0.0861

AC:

13093

AN:

152154

Hom.:

1005

Cov.:

AF XY:

0.0881

AC XY:

6550

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0464

AC:

1928

AN:

41518

American (AMR)

AF:

0.138

AC:

2109

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0548

AC:

190

AN:

3468

East Asian (EAS)

AF:

0.459

AC:

2367

AN:

5158

South Asian (SAS)

AF:

0.0990

AC:

478

AN:

4826

European-Finnish (FIN)

AF:

0.0739

AC:

782

AN:

10584

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0740

AC:

5032

AN:

67998

Other (OTH)

AF:

0.0909

AC:

192

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

560

1120

1681

2241

2801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0795

Hom.:

168

Bravo

AF:

0.0910

Asia WGS

AF:

0.269

AC:

934

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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