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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000680146.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000680146.1		c.208-70207A>C		intron	N/A	ENSP00000505591.1	A0A7P0T9B9

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10511654;

hg19: chr9-18434620;