Genetic Variant NM_080722.4:c.2597-73T>C (chr10-70752022-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_080722.4(ADAMTS14):c.2597-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,550,842 control chromosomes in the GnomAD database, including 54,921 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 0.24 ( 4706 hom., cov: 34)

Exomes 𝑓: 0.26 ( 50215 hom. )

Consequence

ADAMTS14
NM_080722.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.673

Publications

4 publications found

Variant links:

Genes affected

ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

ADAMTS14 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS14	NM_080722.4 link	c.2597-73T>C		intron_variant	Intron 17 of 21	ENST00000373207.2	NP_542453.2	Q8WXS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2 link	c.2597-73T>C		intron_variant	Intron 17 of 21	1	NM_080722.4	ENSP00000362303.1		Q8WXS8-1
ADAMTS14	ENST00000373208.5 link	c.2606-73T>C		intron_variant	Intron 17 of 21	2		ENSP00000362304.1		Q8WXS8-4

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36189

AN:

152038

Hom.:

4701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.259

AC:

362808

AN:

1398686

Hom.:

50215

AF XY:

0.262

AC XY:

180849

AN XY:

689448

show subpopulations

African (AFR)

AF:

0.160

AC:

5129

AN:

32000

American (AMR)

AF:

0.228

AC:

8508

AN:

37302

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

4223

AN:

21818

East Asian (EAS)

AF:

0.586

AC:

22895

AN:

39088

South Asian (SAS)

AF:

0.355

AC:

26741

AN:

75414

European-Finnish (FIN)

AF:

0.274

AC:

13403

AN:

48902

Middle Eastern (MID)

AF:

0.197

AC:

1015

AN:

5162

European-Non Finnish (NFE)

AF:

0.246

AC:

266016

AN:

1081376

Other (OTH)

AF:

0.258

AC:

14878

AN:

57624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

13990

27980

41969

55959

69949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9470

18940

28410

37880

47350

<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:

0.238

AC:

36213

AN:

152156

Hom.:

4706

Cov.:

AF XY:

0.241

AC XY:

17921

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.172

AC:

7159

AN:

41546

American (AMR)

AF:

0.221

AC:

3374

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

713

AN:

3468

East Asian (EAS)

AF:

0.560

AC:

2889

AN:

5158

South Asian (SAS)

AF:

0.362

AC:

1748

AN:

4826

European-Finnish (FIN)

AF:

0.267

AC:

2834

AN:

10602

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16714

AN:

67948

Other (OTH)

AF:

0.236

AC:

499

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1423

2846

4268

5691

7114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.238

Hom.:

743

Bravo

AF:

0.231

Asia WGS

AF:

0.457

AC:

1584

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

(source)

DANN

Benign

0.63

PhyloP100

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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