chr9-18056417-T-C

Variant names:

• chr9-18056417-T-C
• rs1411242
• ENST00000680146.1:c.88-107445T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680146.1(ADAMTSL1):​c.88-107445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,842 control chromosomes in the GnomAD database, including 30,375 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 0.63 (30375 hom., cov: 30)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.142-107445T>C		intron_variant	Intron 2 of 30		XP_011516365.1
ADAMTSL1	XM_017015310.2	c.99+18242T>C		intron_variant	Intron 1 of 29		XP_016870799.1
ADAMTSL1	XM_011518064.4	c.97-107445T>C		intron_variant	Intron 1 of 29		XP_011516366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.88-107445T>C		intron_variant	Intron 1 of 29			ENSP00000505591.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95461 AN: 151724 Hom.: 30343 Cov.: 30

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.629 AC: 95547 AN: 151842 Hom.: 30375 Cov.: 30 AF XY: 0.631 AC XY: 46825 AN XY: 74214

African (AFR) AF: 0.711 AC: 29437 AN: 41388

American (AMR) AF: 0.557 AC: 8496 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1812 AN: 3468

East Asian (EAS) AF: 0.550 AC: 2829 AN: 5142

South Asian (SAS) AF: 0.700 AC: 3366 AN: 4806

European-Finnish (FIN) AF: 0.655 AC: 6909 AN: 10548

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40823 AN: 67934

Other (OTH) AF: 0.565 AC: 1190 AN: 2108

Alfa AF: 0.616 Hom.: 17389

Bravo AF: 0.622

Asia WGS AF: 0.591 AC: 2053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.34
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs1411242; hg19: chr9-18056415;