rs12595247

chr15-100001484-C-T

Variant summary

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

The NM_139057.4(ADAMTS17):c.2592-3895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,680 control chromosomes in the GnomAD database, including 18,863 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 0.49 (18863 hom., cov: 31)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

Genes affected

ADAMTS17 (HGNC:17109): (ADAM metallopeptidase with thrombospondin type 1 motif 17) 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 promote breast cancer cell growth and survival. Mutations in this gene are associated with a Weill-Marchesani-like syndrome, which is characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS17	NM_139057.4	c.2592-3895G>A		intron_variant		ENST00000268070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS17	ENST00000268070.9	c.2592-3895G>A		intron_variant		1	NM_139057.4
ADAMTS17	ENST00000568565.2	c.2673-3895G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73746 AN: 151564 Hom.: 18857 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.486 AC: 73772 AN: 151680 Hom.: 18863 Cov.: 31 AF XY: 0.485 AC XY: 35928 AN XY: 74110

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.485

Alfa AF: 0.560 Hom.: 44498

Bravo AF: 0.472

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.85

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: rs12595247; hg19: chr15-100541689;