rs12784847

Positions:

• chr10-70751772-G-A
• chr10-70751772-G-C

Variant summary

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

The ENST00000373207.2(ADAMTS14):​c.2596+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,304,004 control chromosomes in the GnomAD database, including 45,098 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 0.25 (4749 hom., cov: 32)
  • Exomes 𝑓: 0.26 (40349 hom.)
• Consequence: ADAMTS14 ENST00000373207.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.2596+126G>A		intron_variant		ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.2596+126G>A		intron_variant		1	NM_080722.4	ENSP00000362303	P4
ADAMTS14	ENST00000373208.5	c.2605+126G>A		intron_variant		2		ENSP00000362304	A2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37333 AN: 151998 Hom.: 4752 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.261 AC: 300972 AN: 1151888 Hom.: 40349 AF XY: 0.258 AC XY: 145955 AN XY: 565080

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.246 AC: 37354 AN: 152116 Hom.: 4749 Cov.: 32 AF XY: 0.245 AC XY: 18197 AN XY: 74356

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.249

Alfa AF: 0.261 Hom.: 3444

Bravo AF: 0.245

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12784847; hg19: chr10-72511528; COSMIC: COSV64602536;