ENST00000680146.1:c.207+154775C>G

Variant names:

• chr9-18318756-C-G
• rs9298791
• ENST00000680146.1:c.207+154775C>G

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.207+154775C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,752 control chromosomes in the GnomAD database, including 8,383 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 0.31 (8383 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.261+154775C>G		intron_variant	Intron 3 of 30		XP_011516365.1
ADAMTSL1	XM_017015310.2	c.219+154775C>G		intron_variant	Intron 2 of 29		XP_016870799.1
ADAMTSL1	XM_011518064.4	c.216+154775C>G		intron_variant	Intron 2 of 29		XP_011516366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.207+154775C>G		intron_variant	Intron 2 of 29			ENSP00000505591.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47434 AN: 151632 Hom.: 8373 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.313 AC: 47448 AN: 151752 Hom.: 8383 Cov.: 32 AF XY: 0.318 AC XY: 23556 AN XY: 74134

African (AFR) AF: 0.174 AC: 7203 AN: 41382

American (AMR) AF: 0.502 AC: 7666 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1145 AN: 3462

East Asian (EAS) AF: 0.394 AC: 2034 AN: 5158

South Asian (SAS) AF: 0.422 AC: 2014 AN: 4772

European-Finnish (FIN) AF: 0.332 AC: 3489 AN: 10502

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22913 AN: 67896

Other (OTH) AF: 0.336 AC: 708 AN: 2108

Alfa AF: 0.331 Hom.: 1085

Bravo AF: 0.321

Asia WGS AF: 0.423 AC: 1467 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	0.46
DANN	Benign	0.39
PhyloP100		-0.055

Splicing

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

Other links and lift over

dbSNP: rs9298791; hg19: chr9-18318754;