rs16936441

chr9-18211657-G-A

Variant summary

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

The ENST00000680146.1(ADAMTSL1):c.207+47676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,008 control chromosomes in the GnomAD database, including 2,358 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 0.17 (2358 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	XM_011518063.3	c.261+47676G>A		intron_variant
ADAMTSL1	XM_011518064.4	c.216+47676G>A		intron_variant
ADAMTSL1	XM_017015310.2	c.219+47676G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.207+47676G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26099 AN: 151890 Hom.: 2355 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.172 AC: 26120 AN: 152008 Hom.: 2358 Cov.: 32 AF XY: 0.169 AC XY: 12525 AN XY: 74300

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.190

Alfa AF: 0.179 Hom.: 918

Bravo AF: 0.171

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	4.5
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16936441; hg19: chr9-18211655;