rs11860781

Variant names:

• chr16-77396714-A-T
• rs11860781
• NM_199355.4:c.496-28991T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199355.4(ADAMTS18):​c.496-28991T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,164 control chromosomes in the GnomAD database, including 1,248 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 0.12 (1248 hom., cov: 32)
• Consequence: ADAMTS18 NM_199355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 7 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P
• inherited retinal dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199355.4. 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
	ADAMTS18	NM_199355.4	MANE Select	c.496-28991T>A		intron	N/A	NP_955387.1	Q8TE60-1
	ADAMTS18	NM_001326358.2		c.-25-28991T>A		intron	N/A	NP_001313287.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS18	ENST00000282849.10	TSL:1 MANE Select	c.496-28991T>A		intron	N/A	ENSP00000282849.5	Q8TE60-1
	ADAMTS18	ENST00000562345.1	TSL:5	c.292-29045T>A		intron	N/A	ENSP00000457395.1	H3BTZ3
	ADAMTS18	ENST00000449265.2	TSL:2	n.496-28991T>A		intron	N/A	ENSP00000392540.2	B4DEX3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17897 AN: 152046 Hom.: 1247 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0782

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.118 AC: 17918 AN: 152164 Hom.: 1248 Cov.: 32 AF XY: 0.117 AC XY: 8672 AN XY: 74402

African (AFR) AF: 0.184 AC: 7643 AN: 41504

American (AMR) AF: 0.0783 AC: 1198 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3468

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5184

South Asian (SAS) AF: 0.142 AC: 687 AN: 4822

European-Finnish (FIN) AF: 0.0986 AC: 1043 AN: 10582

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.100 AC: 6832 AN: 67988

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.113 Hom.: 127

Bravo AF: 0.115

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.6
DANN	Benign	0.87
PhyloP100		0.14
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs11860781; hg19: chr16-77430611;