9-18622045-T-G

Variant names:

• chr9-18622045-T-G
• rs10963676
• NM_001040272.6:c.475-198T>G

Variant summary

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

The NM_001040272.6(ADAMTSL1):​c.475-198T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,158 control chromosomes in the GnomAD database, including 1,543 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 0.14 (1543 hom., cov: 32)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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 = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040272.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	NM_001040272.6	MANE Select	c.475-198T>G		intron	N/A	NP_001035362.3
	ADAMTSL1	NM_052866.5		c.475-198T>G		intron	N/A	NP_443098.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.475-198T>G		intron	N/A	ENSP00000369921.4
	ADAMTSL1	ENST00000327883.11	TSL:1	c.475-198T>G		intron	N/A	ENSP00000327887.7
	ADAMTSL1	ENST00000380566.8	TSL:1	c.475-198T>G		intron	N/A	ENSP00000369940.4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20845 AN: 152040 Hom.: 1543 Cov.: 32

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.137 AC: 20858 AN: 152158 Hom.: 1543 Cov.: 32 AF XY: 0.137 AC XY: 10180 AN XY: 74382

African (AFR) AF: 0.0922 AC: 3832 AN: 41540

American (AMR) AF: 0.131 AC: 1996 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1130 AN: 5174

South Asian (SAS) AF: 0.108 AC: 522 AN: 4818

European-Finnish (FIN) AF: 0.175 AC: 1854 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10349 AN: 67982

Other (OTH) AF: 0.141 AC: 297 AN: 2108

Alfa AF: 0.149 Hom.: 7380

Bravo AF: 0.134

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.094
DANN	Benign	0.46
PhyloP100		0.0
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: rs10963676; hg19: chr9-18622043;