rs541686

Positions:

• chr9-18745136-G-A
• chr9-18745136-G-T

Variant summary

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

The NM_001040272.6(ADAMTSL1):​c.2007-8162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,048 control chromosomes in the GnomAD database, including 47,352 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 0.79 (47352 hom., cov: 31)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.2007-8162G>A		intron_variant		ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.2007-8162G>A		intron_variant		5	NM_001040272.6	ENSP00000369921	P1
ADAMTSL1	ENST00000680146.1	c.2151-8162G>A		intron_variant				ENSP00000505591
ADAMTSL1	ENST00000380559.7	n.539-8162G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119707 AN: 151930 Hom.: 47322 Cov.: 31

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.788 AC: 119783 AN: 152048 Hom.: 47352 Cov.: 31 AF XY: 0.783 AC XY: 58225 AN XY: 74334

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.786

Alfa AF: 0.807 Hom.: 6147

Bravo AF: 0.781

Asia WGS AF: 0.702 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.53

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: rs541686; hg19: chr9-18745134;