rs7072645

Variant names:

• chr10-70695794-G-A
• rs7072645
• NM_080722.4:c.523-6518G>A

Variant summary

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

The NM_080722.4(ADAMTS14):​c.523-6518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,280 control chromosomes in the GnomAD database, including 1,671 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 0.11 (1671 hom., cov: 32)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.523-6518G>A		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.523-6518G>A		intron_variant	Intron 2 of 21	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.523-6518G>A		intron_variant	Intron 2 of 21	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16152 AN: 152162 Hom.: 1661 Cov.: 32

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.106 AC: 16178 AN: 152280 Hom.: 1671 Cov.: 32 AF XY: 0.112 AC XY: 8361 AN XY: 74450

African (AFR) AF: 0.0841 AC: 3494 AN: 41566

American (AMR) AF: 0.234 AC: 3585 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3472

East Asian (EAS) AF: 0.540 AC: 2791 AN: 5170

South Asian (SAS) AF: 0.213 AC: 1024 AN: 4812

European-Finnish (FIN) AF: 0.0669 AC: 710 AN: 10620

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0587 AC: 3995 AN: 68030

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.0788 Hom.: 99

Bravo AF: 0.122

Asia WGS AF: 0.305 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		0.0
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: rs7072645; hg19: chr10-72455550;