rs4888622

Positions:

• chr16-77362952-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000282849.10(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 ENST00000282849.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS18	NM_199355.4	c.1057-688A>G		intron_variant		ENST00000282849.10	NP_955387.1
ADAMTS18	NM_001326358.2	c.541-688A>G		intron_variant			NP_001313287.1
ADAMTS18	XM_047433672.1	c.541-688A>G		intron_variant			XP_047289628.1
ADAMTS18	XM_047433673.1	c.-21+850A>G		intron_variant			XP_047289629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS18	ENST00000282849.10	c.1057-688A>G		intron_variant		1	NM_199355.4	ENSP00000282849	P1
ADAMTS18	ENST00000449265.2	c.*235+850A>G		intron_variant, NMD_transcript_variant		2		ENSP00000392540

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

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.522

Alfa AF: 0.565 Hom.: 5385

Bravo AF: 0.527

Asia WGS AF: 0.443 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.4
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs4888622; hg19: chr16-77396849;