rs2210327

Variant names:

• chr9-18109237-A-T
• rs2210327
• ENST00000680146.1:c.88-54625A>T

Variant summary

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

The ENST00000680146.1(ADAMTSL1):​c.88-54625A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 152,092 control chromosomes in the GnomAD database, including 363 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 0.038 (363 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.142-54625A>T		intron_variant	Intron 2 of 30		XP_011516365.1
ADAMTSL1	XM_017015310.2	c.100-54625A>T		intron_variant	Intron 1 of 29		XP_016870799.1
ADAMTSL1	XM_011518064.4	c.97-54625A>T		intron_variant	Intron 1 of 29		XP_011516366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.88-54625A>T		intron_variant	Intron 1 of 29			ENSP00000505591.1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5799 AN: 151974 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.00655

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.0823

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0383

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

GnomAD4 genome AF: 0.0381 AC: 5800 AN: 152092 Hom.: 363 Cov.: 32 AF XY: 0.0395 AC XY: 2935 AN XY: 74334

African (AFR) AF: 0.00653 AC: 271 AN: 41488

American (AMR) AF: 0.0343 AC: 523 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.342 AC: 1758 AN: 5136

South Asian (SAS) AF: 0.0824 AC: 397 AN: 4820

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0356 AC: 2423 AN: 67990

Other (OTH) AF: 0.0384 AC: 81 AN: 2110

Alfa AF: 0.0453 Hom.: 207

Bravo AF: 0.0393

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.49
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs2210327; hg19: chr9-18109235;