10-70716012-A-G

Variant names:

• chr10-70716012-A-G
• rs10823602
• NM_080722.4:c.870+7234A>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.870+7234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,090 control chromosomes in the GnomAD database, including 2,610 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 0.16 (2610 hom., cov: 32)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.870+7234A>G		intron	N/A	NP_542453.2
	ADAMTS14	NM_139155.3		c.870+7234A>G		intron	N/A	NP_631894.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.870+7234A>G		intron	N/A	ENSP00000362303.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.870+7234A>G		intron	N/A	ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24598 AN: 151972 Hom.: 2603 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.162 AC: 24640 AN: 152090 Hom.: 2610 Cov.: 32 AF XY: 0.165 AC XY: 12270 AN XY: 74340

African (AFR) AF: 0.230 AC: 9537 AN: 41450

American (AMR) AF: 0.151 AC: 2309 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3472

East Asian (EAS) AF: 0.559 AC: 2882 AN: 5154

South Asian (SAS) AF: 0.194 AC: 934 AN: 4812

European-Finnish (FIN) AF: 0.113 AC: 1194 AN: 10590

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6989 AN: 68004

Other (OTH) AF: 0.161 AC: 340 AN: 2116

Alfa AF: 0.128 Hom.: 6795

Bravo AF: 0.171

Asia WGS AF: 0.333 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.4
DANN	Benign	0.91
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10823602; hg19: chr10-72475768;