rs75434552

Variant names:

• chr15-100109160-C-T
• rs75434552
• NM_139057.4:c.1889-44G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-100109160-C-T
• chr15-100109160-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139057.4(ADAMTS17):​c.1889-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,572,098 control chromosomes in the GnomAD database, including 475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (26 hom., cov: 33)
  • Exomes 𝑓: 0.013 (449 hom.)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.570
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-100109160-C-T is Benign according to our data. Variant chr15-100109160-C-T is described in ClinVar as Benign. ClinVar VariationId is 1279433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0932 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.1889-44G>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.1889-44G>A		intron	N/A	ENSP00000268070.4	Q8TE56-1
	ADAMTS17	ENST00000961098.1		c.1889-44G>A		intron	N/A	ENSP00000631157.1
	ADAMTS17	ENST00000568565.2	TSL:5	c.1889-44G>A		intron	N/A	ENSP00000456161.2	H3BRA9

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1220 AN: 152062 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00862

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0178 AC: 3198 AN: 179460 AF XY: 0.0228

Gnomad AFR exome AF: 0.00174

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.00217

Gnomad FIN exome AF: 0.00232

Gnomad NFE exome AF: 0.00866

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.0133 AC: 18876 AN: 1419918 Hom.: 449 Cov.: 32 AF XY: 0.0157 AC XY: 11008 AN XY: 702756

African (AFR) AF: 0.00179 AC: 58 AN: 32388

American (AMR) AF: 0.00169 AC: 64 AN: 37768

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 32 AN: 25336

East Asian (EAS) AF: 0.000808 AC: 30 AN: 37142

South Asian (SAS) AF: 0.0892 AC: 7296 AN: 81836

European-Finnish (FIN) AF: 0.00261 AC: 131 AN: 50124

Middle Eastern (MID) AF: 0.0189 AC: 108 AN: 5710

European-Non Finnish (NFE) AF: 0.00950 AC: 10363 AN: 1090722

Other (OTH) AF: 0.0135 AC: 794 AN: 58892

GnomAD4 genome AF: 0.00801 AC: 1219 AN: 152180 Hom.: 26 Cov.: 33 AF XY: 0.00915 AC XY: 681 AN XY: 74398

African (AFR) AF: 0.00145 AC: 60 AN: 41518

American (AMR) AF: 0.00164 AC: 25 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5168

South Asian (SAS) AF: 0.101 AC: 485 AN: 4822

European-Finnish (FIN) AF: 0.00283 AC: 30 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00862 AC: 586 AN: 68006

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

Alfa AF: 0.00450 Hom.: 1

Bravo AF: 0.00524

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.67
PhyloP100		-0.57
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: rs75434552; hg19: chr15-100649365;