rs17600642

Variant names:

• chr10-70703238-C-A
• rs17600642
• NM_080722.4:c.679+770C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-70703238-C-A
• chr10-70703238-C-T

Variant summary

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

The NM_080722.4(ADAMTS14):​c.679+770C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,200 control chromosomes in the GnomAD database, including 1,729 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 0.13 (1729 hom., cov: 33)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.37
• Publications: 12 publications found

Genes affected

ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family 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 enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.679+770C>A		intron_variant	Intron 3 of 21	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.679+770C>A		intron_variant	Intron 3 of 21	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.679+770C>A		intron_variant	Intron 3 of 21	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20439 AN: 152082 Hom.: 1727 Cov.: 33

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.134 AC: 20442 AN: 152200 Hom.: 1729 Cov.: 33 AF XY: 0.132 AC XY: 9804 AN XY: 74400

African (AFR) AF: 0.0529 AC: 2197 AN: 41560

American (AMR) AF: 0.146 AC: 2235 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3472

East Asian (EAS) AF: 0.0625 AC: 323 AN: 5172

South Asian (SAS) AF: 0.147 AC: 708 AN: 4816

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10584

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12347 AN: 67996

Other (OTH) AF: 0.155 AC: 327 AN: 2110

Alfa AF: 0.144 Hom.: 1815

Bravo AF: 0.133

Asia WGS AF: 0.104 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0050
DANN	Benign	0.61
PhyloP100		-4.4
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: rs17600642; hg19: chr10-72462994;