rs11182091

Variant names:

• chr12-43469970-C-T
• rs11182091
• NM_025003.5:c.1118-1265G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAMTS20	NM_025003.5	c.1118-1265G>A		intron_variant	Intron 7 of 38	ENST00000389420.8	NP_079279.3
ADAMTS20	XM_017019979.2	c.-1665G>A		5_prime_UTR_variant	Exon 1 of 32		XP_016875468.1
ADAMTS20	XM_011538754.3	c.1118-1265G>A		intron_variant	Intron 7 of 38		XP_011537056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS20	ENST00000389420.8	c.1118-1265G>A		intron_variant	Intron 7 of 38	1	NM_025003.5	ENSP00000374071.3
ADAMTS20	ENST00000553158.5	c.1118-1265G>A		intron_variant	Intron 7 of 28	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

African (AFR) AF: 0.0207 AC: 859 AN: 41520

American (AMR) AF: 0.135 AC: 2068 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2378 AN: 5172

South Asian (SAS) AF: 0.0992 AC: 478 AN: 4820

European-Finnish (FIN) AF: 0.0743 AC: 788 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5086 AN: 67984

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.0750 Hom.: 1250

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
PhyloP100		-0.48
Mutation Taster		=100/0	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: rs11182091; hg19: chr12-43863773;