10-70697282-C-G

Position:

• chr10-70697282-C-G

Variant summary

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

The NM_080722.4(ADAMTS14):​c.523-5030C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,100 control chromosomes in the GnomAD database, including 30,664 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 (30664 hom., cov: 33)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.523-5030C>G		intron_variant		ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.523-5030C>G		intron_variant		1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.523-5030C>G		intron_variant		2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95860 AN: 151982 Hom.: 30623 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.631 AC: 95953 AN: 152100 Hom.: 30664 Cov.: 33 AF XY: 0.635 AC XY: 47218 AN XY: 74332

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.658

Alfa AF: 0.519 Hom.: 1473

Bravo AF: 0.627

Asia WGS AF: 0.749 AC: 2605 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	0.32
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7081273; hg19: chr10-72457038;