rs13299349

chr9-18573362-G-A

Variant summary

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

The NM_001040272.6(ADAMTSL1):c.238-668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 154,628 control chromosomes in the GnomAD database, including 6,289 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 0.27 (6159 hom., cov: 31)
  • Exomes 𝑓: 0.31 (130 hom.)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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]

MIR3152 (HGNC:38379): (microRNA 3152) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	NM_001040272.6	c.238-668G>A		intron_variant		ENST00000380548.9
MIR3152	NR_036107.1	n.57G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.238-668G>A		intron_variant		5	NM_001040272.6	P1
MIR3152	ENST00000579801.1	n.57G>A		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41261 AN: 151800 Hom.: 6156 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.293

GnomAD3 exomes AF: 0.321 AC: 1927 AN: 6010 Hom.: 319 AF XY: 0.328 AC XY: 936 AN XY: 2856

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.417

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.269

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.306 AC: 829 AN: 2710 Hom.: 130 Cov.: 0 AF XY: 0.303 AC XY: 421 AN XY: 1388

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.272 AC: 41287 AN: 151918 Hom.: 6159 Cov.: 31 AF XY: 0.271 AC XY: 20101 AN XY: 74262

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.289

Alfa AF: 0.289 Hom.: 813

Bravo AF: 0.274

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs13299349; hg19: chr9-18573360;