chr10-70749085-A-G

Variant names:

• chr10-70749085-A-G
• rs10762401
• NM_080722.4:c.2264-737A>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.2264-737A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,062 control chromosomes in the GnomAD database, including 14,072 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 0.41 (14072 hom., cov: 32)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.2264-737A>G		intron	N/A	NP_542453.2	Q8WXS8-1
	ADAMTS14	NM_139155.3		c.2273-737A>G		intron	N/A	NP_631894.2	Q8WXS8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.2264-737A>G		intron	N/A	ENSP00000362303.1	Q8WXS8-1
	ADAMTS14	ENST00000886732.1		c.2273-704A>G		intron	N/A	ENSP00000556791.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.2273-737A>G		intron	N/A	ENSP00000362304.1	Q8WXS8-4

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62182 AN: 151944 Hom.: 14075 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.409 AC: 62196 AN: 152062 Hom.: 14072 Cov.: 32 AF XY: 0.412 AC XY: 30644 AN XY: 74324

African (AFR) AF: 0.203 AC: 8420 AN: 41472

American (AMR) AF: 0.405 AC: 6195 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1456 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3670 AN: 5166

South Asian (SAS) AF: 0.539 AC: 2598 AN: 4822

European-Finnish (FIN) AF: 0.498 AC: 5256 AN: 10560

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33121 AN: 67962

Other (OTH) AF: 0.413 AC: 872 AN: 2110

Alfa AF: 0.454 Hom.: 48099

Bravo AF: 0.391

Asia WGS AF: 0.620 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.60
PhyloP100		0.47
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: rs10762401; hg19: chr10-72508841;