rs1944761

Variant names:

• chr9-18188244-T-C
• rs1944761
• ENST00000680146.1:c.207+24263T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	XM_011518063.3	c.261+24263T>C		intron_variant	Intron 3 of 30		XP_011516365.1
ADAMTSL1	XM_017015310.2	c.219+24263T>C		intron_variant	Intron 2 of 29		XP_016870799.1
ADAMTSL1	XM_011518064.4	c.216+24263T>C		intron_variant	Intron 2 of 29		XP_011516366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000680146.1	c.207+24263T>C		intron_variant	Intron 2 of 29			ENSP00000505591.1

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

African (AFR) AF: 0.689 AC: 28551 AN: 41444

American (AMR) AF: 0.806 AC: 12299 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3892 AN: 5150

South Asian (SAS) AF: 0.808 AC: 3891 AN: 4818

European-Finnish (FIN) AF: 0.827 AC: 8750 AN: 10578

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50391 AN: 67972

Other (OTH) AF: 0.745 AC: 1571 AN: 2110

Alfa AF: 0.742 Hom.: 7306

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
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs1944761; hg19: chr9-18188242;