10-70697554-A-T

Variant names:

• chr10-70697554-A-T
• rs1572798
• NM_080722.4:c.523-4758A>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.523-4758A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,222 control chromosomes in the GnomAD database, including 41,799 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 0.74 (41799 hom., cov: 34)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.523-4758A>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.523-4758A>T		intron_variant	Intron 2 of 21	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.523-4758A>T		intron_variant	Intron 2 of 21	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112334 AN: 152104 Hom.: 41729 Cov.: 34

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.739 AC: 112466 AN: 152222 Hom.: 41799 Cov.: 34 AF XY: 0.740 AC XY: 55036 AN XY: 74420

African (AFR) AF: 0.789 AC: 32754 AN: 41526

American (AMR) AF: 0.773 AC: 11823 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2221 AN: 3468

East Asian (EAS) AF: 0.864 AC: 4469 AN: 5174

South Asian (SAS) AF: 0.828 AC: 4000 AN: 4832

European-Finnish (FIN) AF: 0.652 AC: 6907 AN: 10592

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47789 AN: 68008

Other (OTH) AF: 0.750 AC: 1583 AN: 2112

Alfa AF: 0.630 Hom.: 1984

Bravo AF: 0.748

Asia WGS AF: 0.831 AC: 2891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.47
PhyloP100		-0.30
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: rs1572798; hg19: chr10-72457310;