dbSNP rs737054: FKBP5:c.509-10306C>T (chr6-35607710-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_004117.4(FKBP5):c.509-10306C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 163,258 control chromosomes in the GnomAD database, including 4,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars).

Frequency

Genomes: 𝑓 0.22 ( 4211 hom., cov: 31)

Exomes 𝑓: 0.26 ( 433 hom. )

Consequence

FKBP5
NM_004117.4 intron

Scores

Clinical Significance

Likely risk allele no assertion criteria provided P:1

Conservation

PhyloP100: 0.757

Publications

22 publications found

Variant links:

Genes affected

FKBP5 (HGNC:3721): (FKBP prolyl isomerase 5) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

FKBP5 links:

RPL36P9 (HGNC:36746): (ribosomal protein L36 pseudogene 9)

RPL36P9 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=-0.6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4 link	c.509-10306C>T		intron_variant	Intron 5 of 10	ENST00000357266.9	NP_004108.1	Q13451-1Q2TA84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9 link	c.509-10306C>T		intron_variant	Intron 5 of 10	1	NM_004117.4	ENSP00000349811.3		Q13451-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32717

AN:

151908

Hom.:

4202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0761

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.265

AC:

2973

AN:

11232

Hom.:

433

Cov.:

AF XY:

0.265

AC XY:

1677

AN XY:

6338

show subpopulations

African (AFR)

AF:

0.0549

AC:

AN:

164

American (AMR)

AF:

0.419

AC:

161

AN:

384

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

AN:

East Asian (EAS)

AF:

0.305

AC:

AN:

292

South Asian (SAS)

AF:

0.170

AC:

201

AN:

1180

European-Finnish (FIN)

AF:

0.277

AC:

1390

AN:

5014

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.266

AC:

998

AN:

3758

Other (OTH)

AF:

0.287

AC:

109

AN:

380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

107

214

320

427

534

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:

0.215

AC:

32734

AN:

152026

Hom.:

4211

Cov.:

AF XY:

0.214

AC XY:

15891

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0760

AC:

3154

AN:

41512

American (AMR)

AF:

0.301

AC:

4589

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

992

AN:

3468

East Asian (EAS)

AF:

0.233

AC:

1202

AN:

5148

South Asian (SAS)

AF:

0.157

AC:

751

AN:

4796

European-Finnish (FIN)

AF:

0.273

AC:

2889

AN:

10572

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18318

AN:

67948

Other (OTH)

AF:

0.252

AC:

531

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1242

2484

3727

4969

6211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.263

Hom.:

9949

Bravo

AF:

0.216

Asia WGS

AF:

0.240

AC:

833

AN:

3478

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Susceptibility to severe depressive disorder

Pathogenic:1

Jul 01, 2022

Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology

Significance:Likely risk allele

Review Status:no assertion criteria provided

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.78

(source)

DANN

Benign

0.60

PhyloP100

0.76

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