rs10511654

Variant names:

• chr9-18434622-A-C
• rs10511654
• ENST00000680146.1:c.208-70207A>C

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.208-70207A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 152,282 control chromosomes in the GnomAD database, including 388 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 0.045 (388 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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]

LOC105369293 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.262-70207A>C		intron_variant	Intron 3 of 30		XP_011516365.1
ADAMTSL1	XM_017015310.2	c.220-70207A>C		intron_variant	Intron 2 of 29		XP_016870799.1
ADAMTSL1	XM_011518064.4	c.217-70207A>C		intron_variant	Intron 2 of 29		XP_011516366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.208-70207A>C		intron_variant	Intron 2 of 29			ENSP00000505591.1

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6797 AN: 152164 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0763

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00936

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0448 AC: 6822 AN: 152282 Hom.: 388 Cov.: 32 AF XY: 0.0443 AC XY: 3301 AN XY: 74474

African (AFR) AF: 0.124 AC: 5166 AN: 41546

American (AMR) AF: 0.0269 AC: 411 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5188

South Asian (SAS) AF: 0.0757 AC: 366 AN: 4832

European-Finnish (FIN) AF: 0.00348 AC: 37 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00937 AC: 637 AN: 68018

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0287 Hom.: 60

Bravo AF: 0.0483

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.75
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10511654; hg19: chr9-18434620;