rs2840790

Positions:

• chr9-17969521-C-A
• chr9-17969521-C-G

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.87+62599C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,832 control chromosomes in the GnomAD database, including 19,157 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 0.47 (19157 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	XM_011518063.3	c.141+36496C>A		intron_variant
ADAMTSL1	XM_011518064.4	c.96+62599C>A		intron_variant
ADAMTSL1	XM_017015311.2	c.141+36496C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.87+62599C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71851 AN: 151714 Hom.: 19145 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.473 AC: 71884 AN: 151832 Hom.: 19157 Cov.: 32 AF XY: 0.478 AC XY: 35486 AN XY: 74210

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.476

Alfa AF: 0.523 Hom.: 11873

Bravo AF: 0.470

Asia WGS AF: 0.679 AC: 2357 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2840790; hg19: chr9-17969519;