dbSNP rs1019800: ADAMTS18:c.2532+4544T>G (chr16-77315305-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_199355.4(ADAMTS18):c.2532+4544T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,114 control chromosomes in the GnomAD database, including 10,186 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 0.34 ( 10186 hom., cov: 33)

Consequence

ADAMTS18
NM_199355.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0460

Publications

4 publications found

Variant links:

Genes affected

ADAMTS18 (HGNC:17110): (ADAM metallopeptidase with thrombospondin type 1 motif 18) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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 encoded preproprotein is proteolytically processed to generate the mature protein, which may regulate hemostatic balance and function as a tumor suppressor. Mutations in this gene may be associated with microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) and cone-rod dystrophy in human patients. [provided by RefSeq, May 2016]

ADAMTS18 Gene-Disease associations (from GenCC):

microcornea-myopic chorioretinal atrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
inherited retinal dystrophy
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ADAMTS18 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS18	NM_199355.4 link	c.2532+4544T>G	intron_variant	Intron 16 of 22	ENST00000282849.10	NP_955387.1	Q8TE60-1Q2VYF7Q6ZN25
ADAMTS18	NM_001326358.2 link	c.2016+4544T>G	intron_variant	Intron 16 of 22		NP_001313287.1
ADAMTS18	XM_047433672.1 link	c.2016+4544T>G	intron_variant	Intron 13 of 18		XP_047289628.1
ADAMTS18	XM_047433673.1 link	c.1296+4544T>G	intron_variant	Intron 10 of 16		XP_047289629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS18	ENST00000282849.10 link	c.2532+4544T>G		intron_variant	Intron 16 of 22	1	NM_199355.4	ENSP00000282849.5		Q8TE60-1
ADAMTS18	ENST00000568393.1 link	n.303+4544T>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51542

AN:

151996

Hom.:

10175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.339

AC:

51570

AN:

152114

Hom.:

10186

Cov.:

AF XY:

0.345

AC XY:

25659

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.199

AC:

8260

AN:

41520

American (AMR)

AF:

0.479

AC:

7322

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1242

AN:

3472

East Asian (EAS)

AF:

0.879

AC:

4537

AN:

5162

South Asian (SAS)

AF:

0.400

AC:

1927

AN:

4822

European-Finnish (FIN)

AF:

0.315

AC:

3336

AN:

10588

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.350

AC:

23752

AN:

67954

Other (OTH)

AF:

0.383

AC:

809

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1637

3274

4912

6549

8186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.349

Hom.:

4991

Bravo

AF:

0.351

Asia WGS

AF:

0.619

AC:

2147

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.5

(source)

DANN

Benign

0.66

PhyloP100

-0.046

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