10-70698830-A-G

Variant names:

• chr10-70698830-A-G
• rs1477071
• NM_080722.4:c.523-3482A>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.523-3482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,938 control chromosomes in the GnomAD database, including 11,292 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 0.37 (11292 hom., cov: 32)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• 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 = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.523-3482A>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.523-3482A>G		intron_variant	Intron 2 of 21	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.523-3482A>G		intron_variant	Intron 2 of 21	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56101 AN: 151820 Hom.: 11266 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.370 AC: 56170 AN: 151938 Hom.: 11292 Cov.: 32 AF XY: 0.376 AC XY: 27909 AN XY: 74246

African (AFR) AF: 0.275 AC: 11401 AN: 41412

American (AMR) AF: 0.507 AC: 7746 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1302 AN: 3466

East Asian (EAS) AF: 0.761 AC: 3933 AN: 5170

South Asian (SAS) AF: 0.492 AC: 2364 AN: 4804

European-Finnish (FIN) AF: 0.351 AC: 3706 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24455 AN: 67948

Other (OTH) AF: 0.385 AC: 813 AN: 2112

Alfa AF: 0.371 Hom.: 6597

Bravo AF: 0.377

Asia WGS AF: 0.592 AC: 2060 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	9.3
DANN	Benign	0.79
PhyloP100		0.85
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: rs1477071; hg19: chr10-72458586;