rs10511650

chr9-18005257-C-T

Variant summary

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

The ENST00000680146.1(ADAMTSL1):c.87+98335C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 151,988 control chromosomes in the GnomAD database, including 619 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 0.080 (619 hom., cov: 33)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	XM_011518063.3	c.141+72232C>T		intron_variant
ADAMTSL1	XM_011518064.4	c.96+98335C>T		intron_variant
ADAMTSL1	XM_017015311.2	c.141+72232C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.87+98335C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12169 AN: 151870 Hom.: 613 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.00544

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0802 AC: 12191 AN: 151988 Hom.: 619 Cov.: 33 AF XY: 0.0784 AC XY: 5823 AN XY: 74260

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0411

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.00545

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0571

Gnomad4 OTH AF: 0.0780

Alfa AF: 0.0643 Hom.: 501

Bravo AF: 0.0836

Asia WGS AF: 0.0680 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.5
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10511650; hg19: chr9-18005255;