rs8027190

chr15-100099999-T-Cchr15-100099999-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139057.4(ADAMTS17):c.2017-3523A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,098 control chromosomes in the GnomAD database, including 30,742 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 0.63 (30742 hom., cov: 32)
• Consequence: ADAMTS17 NM_139057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS17	NM_139057.4	c.2017-3523A>G		intron_variant		ENST00000268070.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS17	ENST00000268070.9	c.2017-3523A>G		intron_variant		1	NM_139057.4
ADAMTS17	ENST00000568565.2	c.2017-3523A>G		intron_variant		5		P1
ADAMTS17	ENST00000378898.8	n.1698-3523A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96199 AN: 151980 Hom.: 30707 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.633 AC: 96294 AN: 152098 Hom.: 30742 Cov.: 32 AF XY: 0.635 AC XY: 47255 AN XY: 74360

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.616

Alfa AF: 0.536 Hom.: 2540

Bravo AF: 0.641

Asia WGS AF: 0.663 AC: 2309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs8027190; hg19: chr15-100640204;