chr9-18745136-G-A

Variant names:

• chr9-18745136-G-A
• rs541686
• NM_001040272.6:c.2007-8162G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.81 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	NM_001040272.6	MANE Select	c.2007-8162G>A		intron	N/A	NP_001035362.3	Q8N6G6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.2007-8162G>A		intron	N/A	ENSP00000369921.4	Q8N6G6-3
	ADAMTSL1	ENST00000680146.1		c.2151-8162G>A		intron	N/A	ENSP00000505591.1	A0A7P0T9B9
	ADAMTSL1	ENST00000872893.1		c.1575-8162G>A		intron	N/A	ENSP00000542952.1

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

African (AFR) AF: 0.776 AC: 32184 AN: 41454

American (AMR) AF: 0.736 AC: 11250 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2931 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3109 AN: 5158

South Asian (SAS) AF: 0.766 AC: 3689 AN: 4814

European-Finnish (FIN) AF: 0.806 AC: 8532 AN: 10590

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55455 AN: 67968

Other (OTH) AF: 0.786 AC: 1660 AN: 2112

Alfa AF: 0.806 Hom.: 6376

Bravo AF: 0.781

Asia WGS AF: 0.702 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.53
PhyloP100		0.42
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: rs541686; hg19: chr9-18745134;