rs2830551

Variant names:

• chr21-26843006-C-A
• rs2830551
• NM_006988.5:c.731-321G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant prognathism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAMTS1	NM_006988.5	c.731-321G>T		intron_variant	Intron 1 of 8	ENST00000284984.8	NP_008919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS1	ENST00000284984.8	c.731-321G>T		intron_variant	Intron 1 of 8	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

African (AFR) AF: 0.0297 AC: 143 AN: 4822

American (AMR) AF: 0.282 AC: 1566 AN: 5546

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 654 AN: 5066

East Asian (EAS) AF: 0.0422 AC: 353 AN: 8372

South Asian (SAS) AF: 0.176 AC: 3937 AN: 22362

European-Finnish (FIN) AF: 0.109 AC: 809 AN: 7428

Middle Eastern (MID) AF: 0.151 AC: 111 AN: 736

European-Non Finnish (NFE) AF: 0.131 AC: 13750 AN: 105004

Other (OTH) AF: 0.130 AC: 1216 AN: 9376

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

African (AFR) AF: 0.0320 AC: 1330 AN: 41580

American (AMR) AF: 0.234 AC: 3584 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3470

East Asian (EAS) AF: 0.0553 AC: 286 AN: 5172

South Asian (SAS) AF: 0.180 AC: 867 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1074 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9325 AN: 68014

Other (OTH) AF: 0.150 AC: 317 AN: 2116

Alfa AF: 0.0916 Hom.: 202

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
PhyloP100		1.1
PromoterAI		-0.15	Neutral
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: rs2830551; hg19: chr21-28215325;