rs7862683

Positions:

• chr9-18267949-C-G
• chr9-18267949-C-T

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.207+103968C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,692 control chromosomes in the GnomAD database, including 10,809 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 0.36 (10809 hom., cov: 31)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	XM_011518063.3	c.261+103968C>G		intron_variant
ADAMTSL1	XM_011518064.4	c.216+103968C>G		intron_variant
ADAMTSL1	XM_017015310.2	c.219+103968C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.207+103968C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54760 AN: 151574 Hom.: 10811 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.361 AC: 54763 AN: 151692 Hom.: 10809 Cov.: 31 AF XY: 0.363 AC XY: 26877 AN XY: 74128

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.361

Alfa AF: 0.244 Hom.: 633

Bravo AF: 0.332

Asia WGS AF: 0.387 AC: 1333 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
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: rs7862683; hg19: chr9-18267947;