rs11790127

Variant names:

• chr9-18624302-C-T
• rs11790127
• NM_001040272.6:c.601+1933C>T

Variant summary

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

The NM_001040272.6(ADAMTSL1):​c.601+1933C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,160 control chromosomes in the GnomAD database, including 556 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 0.075 (556 hom., cov: 32)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• 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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.601+1933C>T		intron_variant	Intron 5 of 28	ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.601+1933C>T		intron_variant	Intron 5 of 28	5	NM_001040272.6	ENSP00000369921.4

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11409 AN: 152042 Hom.: 556 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0761

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0750 AC: 11409 AN: 152160 Hom.: 556 Cov.: 32 AF XY: 0.0740 AC XY: 5506 AN XY: 74394

African (AFR) AF: 0.0197 AC: 819 AN: 41510

American (AMR) AF: 0.0760 AC: 1161 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4824

European-Finnish (FIN) AF: 0.0963 AC: 1020 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7709 AN: 67990

Other (OTH) AF: 0.0824 AC: 174 AN: 2112

Alfa AF: 0.0923 Hom.: 114

Bravo AF: 0.0696

Asia WGS AF: 0.0210 AC: 73 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.52
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11790127; hg19: chr9-18624300;