10-70723254-T-C

Variant names:

• chr10-70723254-T-C
• rs1816002
• NM_080722.4:c.871-6040T>C

Variant summary

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

The NM_080722.4(ADAMTS14):​c.871-6040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,952 control chromosomes in the GnomAD database, including 21,284 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 0.52 (21284 hom., cov: 32)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.871-6040T>C		intron	N/A	NP_542453.2
	ADAMTS14	NM_139155.3		c.871-6040T>C		intron	N/A	NP_631894.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.871-6040T>C		intron	N/A	ENSP00000362303.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.871-6040T>C		intron	N/A	ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79239 AN: 151834 Hom.: 21244 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.522 AC: 79340 AN: 151952 Hom.: 21284 Cov.: 32 AF XY: 0.524 AC XY: 38960 AN XY: 74298

African (AFR) AF: 0.630 AC: 26104 AN: 41456

American (AMR) AF: 0.522 AC: 7975 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3468

East Asian (EAS) AF: 0.586 AC: 3024 AN: 5160

South Asian (SAS) AF: 0.673 AC: 3239 AN: 4816

European-Finnish (FIN) AF: 0.455 AC: 4808 AN: 10562

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31181 AN: 67914

Other (OTH) AF: 0.495 AC: 1041 AN: 2104

Alfa AF: 0.479 Hom.: 74433

Bravo AF: 0.529

Asia WGS AF: 0.595 AC: 2072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		0.094
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: rs1816002; hg19: chr10-72483010;