rs7176121

Variant names:

• chr15-100305115-T-C
• rs7176121
• NM_139057.4:c.617-23714A>G

Variant summary

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

The NM_139057.4(ADAMTS17):​c.617-23714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,986 control chromosomes in the GnomAD database, including 32,207 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 0.64 (32207 hom., cov: 31)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• 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: 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 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.617-23714A>G		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.617-23714A>G		intron	N/A	ENSP00000268070.4	Q8TE56-1
	ADAMTS17	ENST00000961098.1		c.617-23714A>G		intron	N/A	ENSP00000631157.1
	ADAMTS17	ENST00000568565.2	TSL:5	c.617-23714A>G		intron	N/A	ENSP00000456161.2	H3BRA9

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97150 AN: 151868 Hom.: 32157 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.640 AC: 97259 AN: 151986 Hom.: 32207 Cov.: 31 AF XY: 0.644 AC XY: 47817 AN XY: 74284

African (AFR) AF: 0.808 AC: 33479 AN: 41460

American (AMR) AF: 0.666 AC: 10183 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3466

East Asian (EAS) AF: 0.561 AC: 2894 AN: 5162

South Asian (SAS) AF: 0.751 AC: 3615 AN: 4816

European-Finnish (FIN) AF: 0.559 AC: 5893 AN: 10546

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37348 AN: 67934

Other (OTH) AF: 0.617 AC: 1304 AN: 2112

Alfa AF: 0.582 Hom.: 13483

Bravo AF: 0.650

Asia WGS AF: 0.686 AC: 2388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.17
PhyloP100		-3.0
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: rs7176121; hg19: chr15-100845320; COSMIC: COSV51494868; COSMIC: COSV51494868;