rs2738

Variant names:

• chr21-26836585-C-A
• rs2738
• NM_006988.5:c.*994G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-26836585-C-A
• chr21-26836585-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.*994G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,560 control chromosomes in the GnomAD database, including 557 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 0.077 (551 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6 hom.)
• Consequence: ADAMTS1 NM_006988.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS1	NM_006988.5	c.*994G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000284984.8	NP_008919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS1	ENST00000284984	c.*994G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_006988.5	ENSP00000284984.2

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11752 AN: 152006 Hom.: 550 Cov.: 32

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0657

GnomAD4 exome AF: 0.173 AC: 76 AN: 440 Hom.: 6 Cov.: 0 AF XY: 0.169 AC XY: 45 AN XY: 266

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0774 AC: 11771 AN: 152120 Hom.: 551 Cov.: 32 AF XY: 0.0774 AC XY: 5756 AN XY: 74348

Gnomad4 AFR AF: 0.0488

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0873

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0666 Hom.: 104

Bravo AF: 0.0706

Asia WGS AF: 0.0940 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.72

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: rs2738; hg19: chr21-28208904;