rs1340043

Positions:

• chr9-18458070-T-C

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.208-46759T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,038 control chromosomes in the GnomAD database, including 35,000 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 0.68 (35000 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516

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 (NFE) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.262-46759T>C		intron_variant			XP_011516365.1
ADAMTSL1	XM_011518064.4	c.217-46759T>C		intron_variant			XP_011516366.1
ADAMTSL1	XM_017015310.2	c.220-46759T>C		intron_variant			XP_016870799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.208-46759T>C		intron_variant				ENSP00000505591

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102997 AN: 151922 Hom.: 34974 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.678 AC: 103071 AN: 152038 Hom.: 35000 Cov.: 32 AF XY: 0.677 AC XY: 50308 AN XY: 74322

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.657

Alfa AF: 0.689 Hom.: 72310

Bravo AF: 0.671

Asia WGS AF: 0.559 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1340043; hg19: chr9-18458068;