NM_001040272.6:c.2007-6986C>T

Variant names:

• chr9-18746312-C-T
• rs10511662
• NM_001040272.6:c.2007-6986C>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.2007-6986C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 152,182 control chromosomes in the GnomAD database, including 793 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 0.070 (793 hom., cov: 32)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6	c.2007-6986C>T		intron_variant	Intron 15 of 28	ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9	c.2007-6986C>T		intron_variant	Intron 15 of 28	5	NM_001040272.6	ENSP00000369921.4
ADAMTSL1	ENST00000680146.1	c.2151-6986C>T		intron_variant	Intron 16 of 29			ENSP00000505591.1
ADAMTSL1	ENST00000380559.7	n.539-6986C>T		intron_variant	Intron 2 of 15	5

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10586 AN: 152064 Hom.: 790 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0696 AC: 10595 AN: 152182 Hom.: 793 Cov.: 32 AF XY: 0.0682 AC XY: 5075 AN XY: 74400

African (AFR) AF: 0.185 AC: 7656 AN: 41466

American (AMR) AF: 0.0419 AC: 641 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0241 AC: 116 AN: 4818

European-Finnish (FIN) AF: 0.0373 AC: 396 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1450 AN: 68028

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0670 Hom.: 104

Bravo AF: 0.0744

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.40
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: rs10511662; hg19: chr9-18746310;