rs4965593

Variant names:

• chr15-100218180-C-G
• rs4965593
• NM_139057.4:c.1076-18757G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-100218180-C-G
• chr15-100218180-C-T

Variant summary

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

The NM_139057.4(ADAMTS17):​c.1076-18757G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,188 control chromosomes in the GnomAD database, including 43,131 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 0.75 (43131 hom., cov: 34)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 10 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS17	NM_139057.4	c.1076-18757G>C		intron_variant	Intron 7 of 21	ENST00000268070.9	NP_620688.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS17	ENST00000268070.9	c.1076-18757G>C		intron_variant	Intron 7 of 21	1	NM_139057.4	ENSP00000268070.4
ADAMTS17	ENST00000568565.2	c.1076-18757G>C		intron_variant	Intron 7 of 22	5		ENSP00000456161.2
ADAMTS17	ENST00000378898.8	n.757-18757G>C		intron_variant	Intron 6 of 14	2
ADAMTS17	ENST00000559976.1	n.72-18757G>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113445 AN: 152070 Hom.: 43075 Cov.: 34

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.746 AC: 113553 AN: 152188 Hom.: 43131 Cov.: 34 AF XY: 0.746 AC XY: 55498 AN XY: 74404

African (AFR) AF: 0.894 AC: 37108 AN: 41528

American (AMR) AF: 0.673 AC: 10300 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2613 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4139 AN: 5168

South Asian (SAS) AF: 0.786 AC: 3794 AN: 4828

European-Finnish (FIN) AF: 0.657 AC: 6938 AN: 10564

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46251 AN: 68014

Other (OTH) AF: 0.722 AC: 1526 AN: 2114

Alfa AF: 0.623 Hom.: 1740

Bravo AF: 0.751

Asia WGS AF: 0.745 AC: 2592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.77
PhyloP100		-1.1
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: rs4965593; hg19: chr15-100758385;