rs11599210

Variant names:

• chr10-70697494-A-G
• rs11599210
• NM_080722.4:c.523-4818A>G

Variant summary

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

The NM_080722.4(ADAMTS14):​c.523-4818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,180 control chromosomes in the GnomAD database, including 14,851 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 0.42 (14851 hom., cov: 33)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 1 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 = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.523-4818A>G		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.523-4818A>G		intron_variant	Intron 2 of 21	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.523-4818A>G		intron_variant	Intron 2 of 21	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64584 AN: 152062 Hom.: 14848 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.425 AC: 64613 AN: 152180 Hom.: 14851 Cov.: 33 AF XY: 0.419 AC XY: 31179 AN XY: 74386

African (AFR) AF: 0.318 AC: 13189 AN: 41520

American (AMR) AF: 0.350 AC: 5347 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1601 AN: 3468

East Asian (EAS) AF: 0.0609 AC: 316 AN: 5186

South Asian (SAS) AF: 0.434 AC: 2089 AN: 4818

European-Finnish (FIN) AF: 0.466 AC: 4927 AN: 10576

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

European-Non Finnish (NFE) AF: 0.522 AC: 35493 AN: 68002

Other (OTH) AF: 0.452 AC: 955 AN: 2112

Alfa AF: 0.472 Hom.: 3887

Bravo AF: 0.406

Asia WGS AF: 0.262 AC: 915 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	0.15
DANN	Benign	0.52
PhyloP100		-1.3
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: rs11599210; hg19: chr10-72457250;