ENST00000680146.1:c.87+8295G>C

Variant names:

• chr9-17915217-G-C
• rs4129864
• ENST00000680146.1:c.87+8295G>C

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.87+8295G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,048 control chromosomes in the GnomAD database, including 40,255 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 0.70 (40255 hom., cov: 31)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.22+7750G>C		intron_variant	Intron 1 of 30		XP_011516365.1
ADAMTSL1	XM_011518064.4	c.96+8295G>C		intron_variant	Intron 1 of 29		XP_011516366.1
ADAMTSL1	XM_017015311.2	c.22+7750G>C		intron_variant	Intron 1 of 29		XP_016870800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.87+8295G>C		intron_variant	Intron 1 of 29			ENSP00000505591.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105797 AN: 151928 Hom.: 40250 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.696 AC: 105817 AN: 152048 Hom.: 40255 Cov.: 31 AF XY: 0.705 AC XY: 52369 AN XY: 74326

African (AFR) AF: 0.359 AC: 14879 AN: 41420

American (AMR) AF: 0.773 AC: 11818 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2783 AN: 3470

East Asian (EAS) AF: 0.973 AC: 5030 AN: 5168

South Asian (SAS) AF: 0.839 AC: 4044 AN: 4820

European-Finnish (FIN) AF: 0.849 AC: 8964 AN: 10560

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55797 AN: 67998

Other (OTH) AF: 0.704 AC: 1485 AN: 2110

Alfa AF: 0.755 Hom.: 5720

Bravo AF: 0.674

Asia WGS AF: 0.825 AC: 2864 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs4129864; hg19: chr9-17915215;