16-77362952-T-C

Variant names:

• chr16-77362952-T-C
• rs4888622
• NM_199355.4:c.1057-688A>G

Variant summary

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

The NM_199355.4(ADAMTS18):​c.1057-688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,934 control chromosomes in the GnomAD database, including 22,275 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 0.54 (22275 hom., cov: 32)
• Consequence: ADAMTS18 NM_199355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 3 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS18	NM_199355.4	MANE Select	c.1057-688A>G		intron	N/A	NP_955387.1
	ADAMTS18	NM_001326358.2		c.541-688A>G		intron	N/A	NP_001313287.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS18	ENST00000282849.10	TSL:1 MANE Select	c.1057-688A>G		intron	N/A	ENSP00000282849.5
	ADAMTS18	ENST00000449265.2	TSL:2	n.*235+850A>G		intron	N/A	ENSP00000392540.2

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81271 AN: 151816 Hom.: 22258 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.535 AC: 81309 AN: 151934 Hom.: 22275 Cov.: 32 AF XY: 0.527 AC XY: 39136 AN XY: 74250

African (AFR) AF: 0.517 AC: 21441 AN: 41444

American (AMR) AF: 0.402 AC: 6129 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2483 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1759 AN: 5182

South Asian (SAS) AF: 0.557 AC: 2680 AN: 4812

European-Finnish (FIN) AF: 0.490 AC: 5158 AN: 10534

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39793 AN: 67922

Other (OTH) AF: 0.522 AC: 1099 AN: 2106

Alfa AF: 0.564 Hom.: 5493

Bravo AF: 0.527

Asia WGS AF: 0.443 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.4
DANN	Benign	0.70
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4888622; hg19: chr16-77396849;