rs776776

chr9-18657560-A-G

Variant summary

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

The NM_001040272.6(ADAMTSL1):c.835-79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,047,626 control chromosomes in the GnomAD database, including 177,598 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 0.55 (23584 hom., cov: 32)
  • Exomes 𝑓: 0.58 (154014 hom.)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54

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]

LOC102724102 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	NM_001040272.6	c.835-79A>G		intron_variant		ENST00000380548.9
LOC102724102	XR_428448.4	n.334T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.835-79A>G		intron_variant		5	NM_001040272.6	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83799 AN: 151860 Hom.: 23590 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.580 AC: 519387 AN: 895648 Hom.: 154014 AF XY: 0.583 AC XY: 270939 AN XY: 464622

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.881

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.552 AC: 83817 AN: 151978 Hom.: 23584 Cov.: 32 AF XY: 0.554 AC XY: 41117 AN XY: 74266

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.556

Alfa AF: 0.561 Hom.: 32320

Bravo AF: 0.556

Asia WGS AF: 0.700 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.010
Dann	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs776776; hg19: chr9-18657558;