rs4129864

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000680146.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000680146.1		c.87+8295G>C		intron	N/A	ENSP00000505591.1	A0A7P0T9B9

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4129864;

hg19: chr9-17915215;