rs402007

Variant summary

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

The NM_006988.5(ADAMTS1):​c.-47G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,477,456 control chromosomes in the GnomAD database, including 427,087 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 0.77 ( 46310 hom., cov: 34)
Exomes 𝑓: 0.75 ( 380777 hom. )

Consequence

ADAMTS1
NM_006988.5 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

Publications

18 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

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=-0.7).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAMTS1NM_006988.5 linkc.-47G>C 5_prime_UTR_variant Exon 1 of 9 ENST00000284984.8 NP_008919.3 Q9UHI8B2RB33

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAMTS1ENST00000284984.8 linkc.-47G>C 5_prime_UTR_variant Exon 1 of 9 1 NM_006988.5 ENSP00000284984.2 Q9UHI8

Frequencies

GnomAD3 genomes
AF:
0.772
AC:
117320
AN:
152056
Hom.:
46256
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.892
Gnomad AMI
AF:
0.679
Gnomad AMR
AF:
0.593
Gnomad ASJ
AF:
0.760
Gnomad EAS
AF:
0.432
Gnomad SAS
AF:
0.692
Gnomad FIN
AF:
0.799
Gnomad MID
AF:
0.633
Gnomad NFE
AF:
0.770
Gnomad OTH
AF:
0.721
GnomAD2 exomes
AF:
0.691
AC:
96054
AN:
138992
AF XY:
0.699
show subpopulations
Gnomad AFR exome
AF:
0.892
Gnomad AMR exome
AF:
0.464
Gnomad ASJ exome
AF:
0.745
Gnomad EAS exome
AF:
0.419
Gnomad FIN exome
AF:
0.781
Gnomad NFE exome
AF:
0.764
Gnomad OTH exome
AF:
0.715
GnomAD4 exome
AF:
0.754
AC:
999600
AN:
1325284
Hom.:
380777
Cov.:
47
AF XY:
0.752
AC XY:
485707
AN XY:
645634
show subpopulations
African (AFR)
AF:
0.900
AC:
25810
AN:
28676
American (AMR)
AF:
0.484
AC:
13372
AN:
27650
Ashkenazi Jewish (ASJ)
AF:
0.751
AC:
14346
AN:
19104
East Asian (EAS)
AF:
0.441
AC:
16588
AN:
37580
South Asian (SAS)
AF:
0.703
AC:
45517
AN:
64778
European-Finnish (FIN)
AF:
0.786
AC:
28877
AN:
36722
Middle Eastern (MID)
AF:
0.641
AC:
3329
AN:
5196
European-Non Finnish (NFE)
AF:
0.772
AC:
810927
AN:
1050680
Other (OTH)
AF:
0.744
AC:
40834
AN:
54898
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
12159
24318
36478
48637
60796
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20186
40372
60558
80744
100930
<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:
0.772
AC:
117426
AN:
152172
Hom.:
46310
Cov.:
34
AF XY:
0.766
AC XY:
57002
AN XY:
74390
show subpopulations
African (AFR)
AF:
0.892
AC:
37061
AN:
41556
American (AMR)
AF:
0.592
AC:
9056
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.760
AC:
2638
AN:
3472
East Asian (EAS)
AF:
0.431
AC:
2215
AN:
5136
South Asian (SAS)
AF:
0.693
AC:
3340
AN:
4818
European-Finnish (FIN)
AF:
0.799
AC:
8473
AN:
10608
Middle Eastern (MID)
AF:
0.647
AC:
189
AN:
292
European-Non Finnish (NFE)
AF:
0.770
AC:
52312
AN:
67978
Other (OTH)
AF:
0.720
AC:
1523
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1347
2694
4040
5387
6734
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
852
1704
2556
3408
4260
<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:
0.772
Hom.:
5360
Bravo
AF:
0.754
Asia WGS
AF:
0.632
AC:
2195
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
10
DANN
Benign
0.87
PhyloP100
0.12
PromoterAI
0.020
Neutral
Mutation Taster
=300/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs402007; hg19: chr21-28217320; COSMIC: COSV53173091; COSMIC: COSV53173091; API