Genetic Variant ADAMTS1:c.*994G>T (chr21-26836585-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006988.5(ADAMTS1):c.*994G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,560 control chromosomes in the GnomAD database, including 557 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 0.077 ( 551 hom., cov: 32)

Exomes 𝑓: 0.17 ( 6 hom. )

Consequence

ADAMTS1
NM_006988.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21

Publications

13 publications found

Variant links:

Genes affected

ADAMTS1 (HGNC:217): (ADAM metallopeptidase with thrombospondin type 1 motif 1) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene contains two disintegrin loops and three C-terminal TS motifs and has anti-angiogenic activity. The expression of this gene may be associated with various inflammatory processes as well as development of cancer cachexia. This gene is likely to be necessary for normal growth, fertility, and organ morphology and function. [provided by RefSeq, Jul 2008]

ADAMTS1 Gene-Disease associations (from GenCC):

autosomal dominant prognathism
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ADAMTS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS1	NM_006988.5 link	c.*994G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000284984.8	NP_008919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS1	ENST00000284984.8 link	c.*994G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_006988.5	ENSP00000284984.2

Frequencies

GnomAD3 genomes

AF:

0.0773

AC:

11752

AN:

152006

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.0519

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.0642

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0873

Gnomad OTH

AF:

0.0657

GnomAD4 exome

AF:

0.173

AC:

AN:

440

Hom.:

Cov.:

AF XY:

0.169

AC XY:

AN XY:

266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.175

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0774

AC:

11771

AN:

152120

Hom.:

551

Cov.:

AF XY:

0.0774

AC XY:

5756

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0488

AC:

2027

AN:

41532

American (AMR)

AF:

0.0529

AC:

809

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0859

AC:

298

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

738

AN:

5162

South Asian (SAS)

AF:

0.0647

AC:

312

AN:

4822

European-Finnish (FIN)

AF:

0.134

AC:

1417

AN:

10540

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0873

AC:

5934

AN:

67998

Other (OTH)

AF:

0.0640

AC:

135

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

556

1113

1669

2226

2782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0700

Hom.:

311

Bravo

AF:

0.0706

Asia WGS

AF:

0.0940

AC:

329

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

2.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over