rs750431

Variant names:

• chr10-70714361-G-A
• rs750431
• NM_080722.4:c.870+5583G>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.870+5583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,212 control chromosomes in the GnomAD database, including 1,914 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 0.14 (1914 hom., cov: 32)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4	c.870+5583G>A		intron_variant	Intron 4 of 21	ENST00000373207.2	NP_542453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.870+5583G>A		intron_variant	Intron 4 of 21	1	NM_080722.4	ENSP00000362303.1
ADAMTS14	ENST00000373208.5	c.870+5583G>A		intron_variant	Intron 4 of 21	2		ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21460 AN: 152094 Hom.: 1912 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.141 AC: 21463 AN: 152212 Hom.: 1914 Cov.: 32 AF XY: 0.138 AC XY: 10277 AN XY: 74404

African (AFR) AF: 0.0544 AC: 2261 AN: 41558

American (AMR) AF: 0.151 AC: 2314 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3470

East Asian (EAS) AF: 0.0624 AC: 322 AN: 5164

South Asian (SAS) AF: 0.149 AC: 718 AN: 4814

European-Finnish (FIN) AF: 0.130 AC: 1380 AN: 10594

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13080 AN: 67992

Other (OTH) AF: 0.164 AC: 346 AN: 2112

Alfa AF: 0.159 Hom.: 307

Bravo AF: 0.139

Asia WGS AF: 0.104 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.60
PhyloP100		2.3
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: rs750431; hg19: chr10-72474117;