NM_006988.5:c.-47G>C

Variant names:

• chr21-26845001-C-G
• rs402007
• NM_006988.5:c.-47G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006988.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS1	NM_006988.5	MANE Select	c.-47G>C		5_prime_UTR	Exon 1 of 9	NP_008919.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS1	ENST00000284984.8	TSL:1 MANE Select	c.-47G>C		5_prime_UTR	Exon 1 of 9	ENSP00000284984.2
	ADAMTS1	ENST00000677958.1		n.-47G>C		non_coding_transcript_exon	Exon 1 of 9	ENSP00000503777.1
	ADAMTS1	ENST00000679316.1		n.409G>C		non_coding_transcript_exon	Exon 1 of 7

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

GnomAD2 exomes AF: 0.691 AC: 96054 AN: 138992 AF XY: 0.699

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 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

African (AFR) AF: 0.900 AC: 25810 AN: 28676

American (AMR) AF: 0.484 AC: 13372 AN: 27650

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 14346 AN: 19104

East Asian (EAS) AF: 0.441 AC: 16588 AN: 37580

South Asian (SAS) AF: 0.703 AC: 45517 AN: 64778

European-Finnish (FIN) AF: 0.786 AC: 28877 AN: 36722

Middle Eastern (MID) AF: 0.641 AC: 3329 AN: 5196

European-Non Finnish (NFE) AF: 0.772 AC: 810927 AN: 1050680

Other (OTH) AF: 0.744 AC: 40834 AN: 54898

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

African (AFR) AF: 0.892 AC: 37061 AN: 41556

American (AMR) AF: 0.592 AC: 9056 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2638 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2215 AN: 5136

South Asian (SAS) AF: 0.693 AC: 3340 AN: 4818

European-Finnish (FIN) AF: 0.799 AC: 8473 AN: 10608

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.770 AC: 52312 AN: 67978

Other (OTH) AF: 0.720 AC: 1523 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		0.12
PromoterAI		0.020	Neutral
Mutation Taster		=300/0	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: rs402007; hg19: chr21-28217320; COSMIC: COSV53173091; COSMIC: COSV53173091;