chr10-70715720-T-C

Variant names:

• chr10-70715720-T-C
• rs736189
• NM_080722.4:c.870+6942T>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.870+6942T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,922 control chromosomes in the GnomAD database, including 36,932 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 0.70 (36932 hom., cov: 31)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.870+6942T>C		intron	N/A	NP_542453.2	Q8WXS8-1
	ADAMTS14	NM_139155.3		c.870+6942T>C		intron	N/A	NP_631894.2	Q8WXS8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.870+6942T>C		intron	N/A	ENSP00000362303.1	Q8WXS8-1
	ADAMTS14	ENST00000886732.1		c.870+6942T>C		intron	N/A	ENSP00000556791.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.870+6942T>C		intron	N/A	ENSP00000362304.1	Q8WXS8-4

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105501 AN: 151802 Hom.: 36881 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.695 AC: 105613 AN: 151922 Hom.: 36932 Cov.: 31 AF XY: 0.695 AC XY: 51575 AN XY: 74254

African (AFR) AF: 0.746 AC: 30891 AN: 41432

American (AMR) AF: 0.628 AC: 9587 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2192 AN: 3472

East Asian (EAS) AF: 0.809 AC: 4166 AN: 5150

South Asian (SAS) AF: 0.769 AC: 3702 AN: 4812

European-Finnish (FIN) AF: 0.636 AC: 6692 AN: 10530

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46040 AN: 67956

Other (OTH) AF: 0.703 AC: 1481 AN: 2106

Alfa AF: 0.675 Hom.: 42825

Bravo AF: 0.693

Asia WGS AF: 0.785 AC: 2730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.50
PhyloP100		-1.6
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: rs736189; hg19: chr10-72475476;