rs17150692

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017946.4(FKBP14):c.165C>T(p.Tyr55Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,612,990 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 47 hom., cov: 33)

Exomes 𝑓: 0.018 ( 357 hom. )

Consequence

FKBP14
NM_017946.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.81

Publications

7 publications found

Variant links:

Genes affected

FKBP14 (HGNC:18625): (FKBP prolyl isomerase 14) The protein encoded by this gene is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases. The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding. Defects in this gene are a cause of a type of Ehlers-Danlos syndrome (EDS). Both a protein-coding variant and noncoding variants are transcribed from this gene. [provided by RefSeq, Mar 2012]

FKBP14 links:

FKBP14-AS1 (HGNC:40990): (FKBP14 antisense RNA 1)

FKBP14-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 7-30026344-G-A is Benign according to our data. Variant chr7-30026344-G-A is described in ClinVar as Benign. ClinVar VariationId is 384694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.81 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP14	NM_017946.4 link	c.165C>T	p.Tyr55Tyr	synonymous_variant	Exon 1 of 4	ENST00000222803.10	NP_060416.1	Q9NWM8A0A090N7V8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP14	ENST00000222803.10 link	c.165C>T	p.Tyr55Tyr	synonymous_variant	Exon 1 of 4	1	NM_017946.4	ENSP00000222803.5		Q9NWM8

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2954

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.0406

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0245

AC:

6149

AN:

250820

AF XY:

0.0229

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.0616

Gnomad ASJ exome

AF:

0.0370

Gnomad EAS exome

AF:

0.0374

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.0163

Gnomad OTH exome

AF:

0.0229

GnomAD4 exome

AF:

0.0185

AC:

27013

AN:

1460690

Hom.:

357

Cov.:

AF XY:

0.0183

AC XY:

13273

AN XY:

726726

show subpopulations

African (AFR)

AF:

0.0192

AC:

641

AN:

33380

American (AMR)

AF:

0.0596

AC:

2653

AN:

44478

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

1022

AN:

26096

East Asian (EAS)

AF:

0.0444

AC:

1763

AN:

39684

South Asian (SAS)

AF:

0.0207

AC:

1785

AN:

86188

European-Finnish (FIN)

AF:

0.00212

AC:

113

AN:

53400

Middle Eastern (MID)

AF:

0.0252

AC:

145

AN:

5758

European-Non Finnish (NFE)

AF:

0.0159

AC:

17631

AN:

1111386

Other (OTH)

AF:

0.0209

AC:

1260

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1339

2678

4018

5357

6696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.0194

AC:

2955

AN:

152300

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1425

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0198

AC:

824

AN:

41560

American (AMR)

AF:

0.0377

AC:

577

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

149

AN:

3472

East Asian (EAS)

AF:

0.0405

AC:

210

AN:

5188

South Asian (SAS)

AF:

0.0214

AC:

103

AN:

4822

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0153

AC:

1038

AN:

68018

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

144

288

432

576

720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0185

Hom.:

Bravo

AF:

0.0232

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0166

EpiControl

AF:

0.0198

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome

Benign:1

Jul 16, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, kyphoscoliotic type, 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 04, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.8

PromoterAI

-0.047

Neutral

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over