rs10963578

Positions:

• chr9-18338651-G-A

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.208-166178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,902 control chromosomes in the GnomAD database, including 4,165 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 0.22 (4165 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	XM_011518063.3	c.262-166178G>A		intron_variant
ADAMTSL1	XM_011518064.4	c.217-166178G>A		intron_variant
ADAMTSL1	XM_017015310.2	c.220-166178G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.208-166178G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32720 AN: 151784 Hom.: 4150 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.216 AC: 32741 AN: 151902 Hom.: 4165 Cov.: 32 AF XY: 0.221 AC XY: 16415 AN XY: 74228

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.226

Alfa AF: 0.217 Hom.: 490

Bravo AF: 0.232

Asia WGS AF: 0.311 AC: 1079 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	1.5
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10963578; hg19: chr9-18338649;