9-17979580-T-C

Variant names:

• chr9-17979580-T-C
• rs1755271
• ENST00000680146.1:c.87+72658T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680146.1(ADAMTSL1):​c.87+72658T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,206 control chromosomes in the GnomAD database, including 23,072 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 0.53 (23072 hom., cov: 29)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.141+46555T>C		intron_variant	Intron 2 of 30		XP_011516365.1
ADAMTSL1	XM_011518064.4	c.96+72658T>C		intron_variant	Intron 1 of 29		XP_011516366.1
ADAMTSL1	XM_017015311.2	c.141+46555T>C		intron_variant	Intron 2 of 29		XP_016870800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.87+72658T>C		intron_variant	Intron 1 of 29			ENSP00000505591.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80211 AN: 151086 Hom.: 23062 Cov.: 29

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.419

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.531 AC: 80252 AN: 151206 Hom.: 23072 Cov.: 29 AF XY: 0.536 AC XY: 39563 AN XY: 73838

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.528

Alfa AF: 0.573 Hom.: 10152

Bravo AF: 0.529

Asia WGS AF: 0.703 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.3
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1755271; hg19: chr9-17979578;