rs11182091

Positions:

• chr12-43469970-C-T

Variant summary

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

The NM_025003.5(ADAMTS20):​c.1118-1265G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,164 control chromosomes in the GnomAD database, including 976 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 0.079 (976 hom., cov: 33)
• Consequence: ADAMTS20 NM_025003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS20	NM_025003.5	c.1118-1265G>A		intron_variant		ENST00000389420.8	NP_079279.3
ADAMTS20	XM_017019979.2	c.-1665G>A		5_prime_UTR_variant	1/32		XP_016875468.1
ADAMTS20	XM_011538754.3	c.1118-1265G>A		intron_variant			XP_011537056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS20	ENST00000389420.8	c.1118-1265G>A		intron_variant		1	NM_025003.5	ENSP00000374071.3
ADAMTS20	ENST00000553158.5	c.1118-1265G>A		intron_variant		5		ENSP00000448341.1

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12039 AN: 152046 Hom.: 972 Cov.: 33

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0828

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0792 AC: 12048 AN: 152164 Hom.: 976 Cov.: 33 AF XY: 0.0815 AC XY: 6064 AN XY: 74402

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.0992

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.0876

Alfa AF: 0.0757 Hom.: 671

Bravo AF: 0.0835

Asia WGS AF: 0.267 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.73

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: rs11182091; hg19: chr12-43863773;