rs4694123

Positions:

• chr4-72522071-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014243.3(ADAMTS3):​c.504+26407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,026 control chromosomes in the GnomAD database, including 5,065 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 0.25 (5065 hom., cov: 32)
• Consequence: ADAMTS3 NM_014243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824

Genes affected

ADAMTS3 (HGNC:219): (ADAM metallopeptidase with thrombospondin type 1 motif 3) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 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 protease. This protease, a member of the procollagen aminopropeptidase subfamily of proteins, may play a role in the processing of type II fibrillar collagen in articular cartilage. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS3	NM_014243.3	c.504+26407A>G		intron_variant		ENST00000286657.10
ADAMTS3	XM_011532421.2	c.447+26407A>G		intron_variant
ADAMTS3	XM_011532422.4	c.420+26407A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS3	ENST00000286657.10	c.504+26407A>G		intron_variant		1	NM_014243.3	P1
ADAMTS3	ENST00000505193.1	n.461+26407A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38550 AN: 151908 Hom.: 5057 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.254 AC: 38573 AN: 152026 Hom.: 5065 Cov.: 32 AF XY: 0.254 AC XY: 18878 AN XY: 74280

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.261

Alfa AF: 0.267 Hom.: 1068

Bravo AF: 0.255

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs4694123; hg19: chr4-73387788;