rs1079351

Positions:

• chr10-70693576-C-A
• chr10-70693576-C-T

Variant summary

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

The NM_080722.4(ADAMTS14):​c.523-8736C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,162 control chromosomes in the GnomAD database, including 4,556 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 0.22 (4556 hom., cov: 32)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.523-8736C>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.523-8736C>A		intron_variant		1	NM_080722.4	ENSP00000362303	P4
ADAMTS14	ENST00000373208.5	c.523-8736C>A		intron_variant		2		ENSP00000362304	A2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34102 AN: 152044 Hom.: 4557 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.224 AC: 34107 AN: 152162 Hom.: 4556 Cov.: 32 AF XY: 0.224 AC XY: 16659 AN XY: 74378

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.243

Alfa AF: 0.263 Hom.: 5476

Bravo AF: 0.210

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.64

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: rs1079351; hg19: chr10-72453332;