Genetic Variant NM_001040272.6:c.835-79A>G (chr9-18657560-A-G) – 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.835-79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,047,626 control chromosomes in the GnomAD database, including 177,598 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 0.55 ( 23584 hom., cov: 32)

Exomes 𝑓: 0.58 ( 154014 hom. )

Consequence

ADAMTSL1
NM_001040272.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.54

Publications

6 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:

ENSG00000304884 (HGNC:):

ENSG00000304884 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL1	NM_001040272.6 link	c.835-79A>G		intron_variant	Intron 7 of 28	ENST00000380548.9	NP_001035362.3	Q8N6G6-3Q6MZQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL1	ENST00000380548.9 link	c.835-79A>G		intron_variant	Intron 7 of 28	5	NM_001040272.6	ENSP00000369921.4		Q8N6G6-3

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83799

AN:

151860

Hom.:

23590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.605

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.559

GnomAD4 exome

AF:

0.580

AC:

519387

AN:

895648

Hom.:

154014

AF XY:

0.583

AC XY:

270939

AN XY:

464622

show subpopulations

African (AFR)

AF:

0.454

AC:

10319

AN:

22754

American (AMR)

AF:

0.671

AC:

26355

AN:

39300

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

10505

AN:

21300

East Asian (EAS)

AF:

0.881

AC:

32183

AN:

36530

South Asian (SAS)

AF:

0.668

AC:

46345

AN:

69386

European-Finnish (FIN)

AF:

0.544

AC:

26939

AN:

49498

Middle Eastern (MID)

AF:

0.570

AC:

2550

AN:

4472

European-Non Finnish (NFE)

AF:

0.558

AC:

340448

AN:

610664

Other (OTH)

AF:

0.569

AC:

23743

AN:

41744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

10488

20975

31463

41950

52438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6992

13984

20976

27968

34960

<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:

0.552

AC:

83817

AN:

151978

Hom.:

23584

Cov.:

AF XY:

0.554

AC XY:

41117

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.467

AC:

19348

AN:

41440

American (AMR)

AF:

0.623

AC:

9522

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

1681

AN:

3470

East Asian (EAS)

AF:

0.882

AC:

4551

AN:

5158

South Asian (SAS)

AF:

0.666

AC:

3207

AN:

4814

European-Finnish (FIN)

AF:

0.542

AC:

5720

AN:

10554

Middle Eastern (MID)

AF:

0.599

AC:

175

AN:

292

European-Non Finnish (NFE)

AF:

0.558

AC:

37933

AN:

67944

Other (OTH)

AF:

0.556

AC:

1176

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1935

3870

5805

7740

9675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.561

Hom.:

45124

Bravo

AF:

0.556

Asia WGS

AF:

0.700

AC:

2430

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.010

(source)

DANN

Benign

0.25

PhyloP100

-3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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