chr15-100317450-C-T

Variant names:

• chr15-100317450-C-T
• rs8029650
• NM_139057.4:c.616+13439G>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.616+13439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 152,178 control chromosomes in the GnomAD database, including 219 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 0.040 (219 hom., cov: 32)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 1 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS17	NM_139057.4	c.616+13439G>A		intron_variant	Intron 3 of 21	ENST00000268070.9	NP_620688.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS17	ENST00000268070.9	c.616+13439G>A		intron_variant	Intron 3 of 21	1	NM_139057.4	ENSP00000268070.4

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6081 AN: 152060 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0401 AC: 6099 AN: 152178 Hom.: 219 Cov.: 32 AF XY: 0.0399 AC XY: 2969 AN XY: 74410

African (AFR) AF: 0.0930 AC: 3860 AN: 41516

American (AMR) AF: 0.0199 AC: 304 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.0432 AC: 223 AN: 5164

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4822

European-Finnish (FIN) AF: 0.0220 AC: 233 AN: 10610

Middle Eastern (MID) AF: 0.0345 AC: 10 AN: 290

European-Non Finnish (NFE) AF: 0.0175 AC: 1187 AN: 67984

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0249 Hom.: 117

Bravo AF: 0.0422

Asia WGS AF: 0.0330 AC: 113 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	1.8
DANN	Benign	0.70
PhyloP100		-0.37
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: rs8029650; hg19: chr15-100857655;