rs11182085

Positions:

• chr12-43453880-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_025003.5(ADAMTS20):​c.1760+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 1,565,280 control chromosomes in the GnomAD database, including 9,713 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 0.086 (1005 hom., cov: 32)
  • Exomes 𝑓: 0.091 (8708 hom.)
• Consequence: ADAMTS20 NM_025003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

Genes affected

ADAMTS20 (HGNC:17178): (ADAM metallopeptidase with thrombospondin type 1 motif 20) The protein encoded by this gene is a member of the ADAMTS family of zinc-dependent proteases. The encoded protein has a signal peptide that is cleaved to release the mature peptide, which is secreted and found in the extracellular matrix. This protein may be involved in tissue remodeling. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS20	NM_025003.5	c.1760+27T>C		intron_variant		ENST00000389420.8	NP_079279.3
ADAMTS20	XM_011538754.3	c.1763+27T>C		intron_variant			XP_011537056.1
ADAMTS20	XM_017019979.2	c.548+27T>C		intron_variant			XP_016875468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS20	ENST00000389420.8	c.1760+27T>C		intron_variant		1	NM_025003.5	ENSP00000374071	P1
ADAMTS20	ENST00000553158.5	c.1760+27T>C		intron_variant		5		ENSP00000448341

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13080 AN: 152036 Hom.: 1001 Cov.: 32

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.0861

GnomAD3 exomes AF: 0.119 AC: 21628 AN: 181322 Hom.: 2472 AF XY: 0.114 AC XY: 10987 AN XY: 96098

Gnomad AFR exome AF: 0.0440

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.0574

Gnomad EAS exome AF: 0.490

Gnomad SAS exome AF: 0.0850

Gnomad FIN exome AF: 0.0764

Gnomad NFE exome AF: 0.0762

Gnomad OTH exome AF: 0.0969

GnomAD4 exome AF: 0.0910 AC: 128656 AN: 1413126 Hom.: 8708 Cov.: 31 AF XY: 0.0903 AC XY: 63071 AN XY: 698580

Gnomad4 AFR exome AF: 0.0415

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.0572

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.0997

GnomAD4 genome AF: 0.0861 AC: 13093 AN: 152154 Hom.: 1005 Cov.: 32 AF XY: 0.0881 AC XY: 6550 AN XY: 74382

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.0739

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0909

Alfa AF: 0.0795 Hom.: 168

Bravo AF: 0.0910

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11182085; hg19: chr12-43847683; COSMIC: COSV67131539;