rs748165

Variant names:

• chr10-70700899-C-T
• rs748165
• NM_080722.4:c.523-1413C>T

Variant summary

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

The NM_080722.4(ADAMTS14):​c.523-1413C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,192 control chromosomes in the GnomAD database, including 2,621 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 0.16 (2621 hom., cov: 33)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.523-1413C>T		intron_variant	Intron 2 of 21	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.523-1413C>T		intron_variant	Intron 2 of 21	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.523-1413C>T		intron_variant	Intron 2 of 21	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25039 AN: 152074 Hom.: 2618 Cov.: 33

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.165 AC: 25045 AN: 152192 Hom.: 2621 Cov.: 33 AF XY: 0.161 AC XY: 11983 AN XY: 74404

African (AFR) AF: 0.0610 AC: 2532 AN: 41538

American (AMR) AF: 0.160 AC: 2444 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3466

East Asian (EAS) AF: 0.0455 AC: 236 AN: 5192

South Asian (SAS) AF: 0.153 AC: 738 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1896 AN: 10574

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15732 AN: 67992

Other (OTH) AF: 0.180 AC: 379 AN: 2108

Alfa AF: 0.206 Hom.: 2027

Bravo AF: 0.158

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.047
DANN	Benign	0.39
PhyloP100		-2.0
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: rs748165; hg19: chr10-72460655;