rs16945612

chr16-77395075-T-C

Variant summary

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

The NM_199355.4(ADAMTS18):c.496-27352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,160 control chromosomes in the GnomAD database, including 1,608 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 0.13 (1608 hom., cov: 32)
• Consequence: ADAMTS18 NM_199355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS18	NM_199355.4	c.496-27352A>G		intron_variant		ENST00000282849.10
ADAMTS18	NM_001326358.2	c.-25-27352A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS18	ENST00000282849.10	c.496-27352A>G		intron_variant		1	NM_199355.4	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19617 AN: 152042 Hom.: 1604 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.129 AC: 19656 AN: 152160 Hom.: 1608 Cov.: 32 AF XY: 0.128 AC XY: 9549 AN XY: 74386

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0797

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.0361

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0983

Gnomad4 NFE AF: 0.0999

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0982 Hom.: 1438

Bravo AF: 0.127

Asia WGS AF: 0.115 AC: 403 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	0.80
Dann	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs16945612; hg19: chr16-77428972;