rs402007

chr21-26845001-C-Gchr21-26845001-C-T

Variant summary

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

The NM_006988.5(ADAMTS1):c.-47G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,477,456 control chromosomes in the GnomAD database, including 427,087 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 0.77 (46310 hom., cov: 34)
  • Exomes 𝑓: 0.75 (380777 hom.)
• Consequence: ADAMTS1 NM_006988.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS1	NM_006988.5	c.-47G>C		5_prime_UTR_variant	1/9	ENST00000284984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS1	ENST00000284984.8	c.-47G>C		5_prime_UTR_variant	1/9	1	NM_006988.5	P1
ADAMTS1	ENST00000676955.1	c.-47G>C		5_prime_UTR_variant	1/8
ADAMTS1	ENST00000679316.1	n.409G>C		non_coding_transcript_exon_variant	1/7
ADAMTS1	ENST00000677958.1	c.-47G>C		5_prime_UTR_variant, NMD_transcript_variant	1/9

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117320 AN: 152056 Hom.: 46256 Cov.: 34

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.721

GnomAD3 exomes AF: 0.691 AC: 96054 AN: 138992 Hom.: 34544 AF XY: 0.699 AC XY: 53010 AN XY: 75870

Gnomad AFR exome AF: 0.892

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.745

Gnomad EAS exome AF: 0.419

Gnomad SAS exome AF: 0.694

Gnomad FIN exome AF: 0.781

Gnomad NFE exome AF: 0.764

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.754 AC: 999600 AN: 1325284 Hom.: 380777 Cov.: 47 AF XY: 0.752 AC XY: 485707 AN XY: 645634

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.751

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.703

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.772 AC: 117426 AN: 152172 Hom.: 46310 Cov.: 34 AF XY: 0.766 AC XY: 57002 AN XY: 74390

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.720

Alfa AF: 0.772 Hom.: 5360

Bravo AF: 0.754

Asia WGS AF: 0.632 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	10
Dann	Benign	0.87

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: rs402007; hg19: chr21-28217320; COSMIC: COSV53173091; COSMIC: COSV53173091;