rs1944761

chr9-18188244-T-C

Variant summary

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

The ENST00000680146.1(ADAMTSL1):c.207+24263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,010 control chromosomes in the GnomAD database, including 41,986 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 0.74 (41986 hom., cov: 32)
• Consequence: ADAMTSL1 ENST00000680146.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	XM_011518063.3	c.261+24263T>C		intron_variant
ADAMTSL1	XM_011518064.4	c.216+24263T>C		intron_variant
ADAMTSL1	XM_017015310.2	c.219+24263T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.207+24263T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112652 AN: 151892 Hom.: 41965 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.741 AC: 112715 AN: 152010 Hom.: 41986 Cov.: 32 AF XY: 0.749 AC XY: 55631 AN XY: 74298

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.806

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.745

Alfa AF: 0.744 Hom.: 7121

Bravo AF: 0.737

Asia WGS AF: 0.789 AC: 2743 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	0.21
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1944761; hg19: chr9-18188242;