dbSNP rs13299349: ADAMTSL1:c.238-668G>A (chr9-18573362-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001040272.6(ADAMTSL1):c.238-668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 154,628 control chromosomes in the GnomAD database, including 6,289 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 0.27 ( 6159 hom., cov: 31)

Exomes 𝑓: 0.31 ( 130 hom. )

Consequence

ADAMTSL1
NM_001040272.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0370

Publications

17 publications found

Variant links:

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]

ADAMTSL1 links:

MIR3152 (HGNC:38379): (microRNA 3152) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3152 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6 link	c.238-668G>A		intron_variant	Intron 3 of 28	ENST00000380548.9	NP_001035362.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9 link	c.238-668G>A		intron_variant	Intron 3 of 28	5	NM_001040272.6	ENSP00000369921.4

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41261

AN:

151800

Hom.:

6156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.321

AC:

1927

AN:

6010

AF XY:

0.328

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.125

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.306

AC:

829

AN:

2710

Hom.:

130

Cov.:

AF XY:

0.303

AC XY:

421

AN XY:

1388

show subpopulations

African (AFR)

AF:

0.216

AC:

AN:

American (AMR)

AF:

0.375

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.229

AC:

AN:

European-Finnish (FIN)

AF:

0.305

AC:

130

AN:

426

Middle Eastern (MID)

AF:

0.323

AC:

527

AN:

1632

European-Non Finnish (NFE)

AF:

0.298

AC:

AN:

262

Other (OTH)

AF:

0.247

AC:

AN:

198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.272

AC:

41287

AN:

151918

Hom.:

6159

Cov.:

AF XY:

0.271

AC XY:

20101

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.169

AC:

7014

AN:

41442

American (AMR)

AF:

0.359

AC:

5496

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1463

AN:

3464

East Asian (EAS)

AF:

0.122

AC:

626

AN:

5132

South Asian (SAS)

AF:

0.274

AC:

1316

AN:

4800

European-Finnish (FIN)

AF:

0.263

AC:

2778

AN:

10562

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.318

AC:

21622

AN:

67912

Other (OTH)

AF:

0.289

AC:

611

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1505

3011

4516

6022

7527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.289

Hom.:

813

Bravo

AF:

0.274

Asia WGS

AF:

0.202

AC:

703

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

1.2

(source)

DANN

Benign

0.37

PhyloP100

0.037

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over