rs2830551

Positions:

• chr21-26843006-C-A

Variant summary

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

The NM_006988.5(ADAMTS1):​c.731-321G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 320,992 control chromosomes in the GnomAD database, including 3,166 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 0.11 (1395 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1771 hom.)
• Consequence: ADAMTS1 NM_006988.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

ADAMTS1 (HGNC:217): (ADAM metallopeptidase with thrombospondin type 1 motif 1) 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 protein encoded by this gene contains two disintegrin loops and three C-terminal TS motifs and has anti-angiogenic activity. The expression of this gene may be associated with various inflammatory processes as well as development of cancer cachexia. This gene is likely to be necessary for normal growth, fertility, and organ morphology and function. [provided by RefSeq, Jul 2008]

ADAMTS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS1	NM_006988.5	c.731-321G>T		intron_variant		ENST00000284984.8	NP_008919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS1	ENST00000284984.8	c.731-321G>T		intron_variant		1	NM_006988.5	ENSP00000284984.2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17427 AN: 152162 Hom.: 1396 Cov.: 33

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0554

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.134 AC: 22539 AN: 168712 Hom.: 1771 Cov.: 0 AF XY: 0.136 AC XY: 12124 AN XY: 89058

Gnomad4 AFR exome AF: 0.0297

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.0422

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.114 AC: 17435 AN: 152280 Hom.: 1395 Cov.: 33 AF XY: 0.115 AC XY: 8580 AN XY: 74450

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0553

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.150

Alfa AF: 0.123 Hom.: 168

Bravo AF: 0.123

Asia WGS AF: 0.133 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.90

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: rs2830551; hg19: chr21-28215325;