15-100208916-C-T

Variant names:

• chr15-100208916-C-T
• rs1480952
• NM_139057.4:c.1076-9493G>A

Variant summary

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

The NM_139057.4(ADAMTS17):​c.1076-9493G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,856 control chromosomes in the GnomAD database, including 35,625 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 0.68 (35625 hom., cov: 30)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 5 publications found

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]

ADAMTS17 Gene-Disease associations (from GenCC):

• Weill-Marchesani 4 syndrome, recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Orphanet, Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139057.4. 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
	ADAMTS17	NM_139057.4	MANE Select	c.1076-9493G>A		intron	N/A	NP_620688.2	Q8TE56-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS17	ENST00000268070.9	TSL:1 MANE Select	c.1076-9493G>A		intron	N/A	ENSP00000268070.4	Q8TE56-1
	ADAMTS17	ENST00000961098.1		c.1076-9493G>A		intron	N/A	ENSP00000631157.1
	ADAMTS17	ENST00000568565.2	TSL:5	c.1076-9493G>A		intron	N/A	ENSP00000456161.2	H3BRA9

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103659 AN: 151738 Hom.: 35618 Cov.: 30

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.683 AC: 103699 AN: 151856 Hom.: 35625 Cov.: 30 AF XY: 0.683 AC XY: 50692 AN XY: 74204

African (AFR) AF: 0.657 AC: 27181 AN: 41398

American (AMR) AF: 0.643 AC: 9818 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2204 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2916 AN: 5138

South Asian (SAS) AF: 0.741 AC: 3565 AN: 4810

European-Finnish (FIN) AF: 0.715 AC: 7540 AN: 10540

Middle Eastern (MID) AF: 0.676 AC: 196 AN: 290

European-Non Finnish (NFE) AF: 0.710 AC: 48232 AN: 67926

Other (OTH) AF: 0.675 AC: 1419 AN: 2102

Alfa AF: 0.698 Hom.: 37810

Bravo AF: 0.676

Asia WGS AF: 0.679 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.35
PhyloP100		-1.6
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: rs1480952; hg19: chr15-100749121;