9-18650111-A-G

Variant names:

• chr9-18650111-A-G
• rs13286493
• NM_001040272.6:c.835-7528A>G

Variant summary

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

The NM_001040272.6(ADAMTSL1):​c.835-7528A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,156 control chromosomes in the GnomAD database, including 1,373 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 0.12 (1373 hom., cov: 32)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.03
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040272.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	NM_001040272.6	MANE Select	c.835-7528A>G		intron	N/A	NP_001035362.3
	ADAMTSL1	NM_052866.5		c.835-7528A>G		intron	N/A	NP_443098.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.835-7528A>G		intron	N/A	ENSP00000369921.4
	ADAMTSL1	ENST00000327883.11	TSL:1	c.835-7528A>G		intron	N/A	ENSP00000327887.7
	ADAMTSL1	ENST00000380566.8	TSL:1	c.835-7528A>G		intron	N/A	ENSP00000369940.4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18705 AN: 152038 Hom.: 1371 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.123 AC: 18709 AN: 152156 Hom.: 1373 Cov.: 32 AF XY: 0.120 AC XY: 8900 AN XY: 74382

African (AFR) AF: 0.0673 AC: 2796 AN: 41550

American (AMR) AF: 0.127 AC: 1937 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5166

South Asian (SAS) AF: 0.0285 AC: 137 AN: 4814

European-Finnish (FIN) AF: 0.156 AC: 1655 AN: 10588

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11227 AN: 67966

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.0593 Hom.: 54

Bravo AF: 0.119

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.23
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13286493; hg19: chr9-18650109;