Genetic Variant FKBP5:c.841-238C>A (chr6-35580459-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004117.4(FKBP5):c.841-238C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FKBP5
NM_004117.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.960

Publications

30 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:

ENSG00000228559 (HGNC:58100):

ENSG00000228559 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FKBP5	NM_004117.4 link	c.841-238C>A	intron_variant	Intron 8 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3 link	c.841-238C>A	intron_variant	Intron 9 of 11		NP_001139247.1
FKBP5	NM_001145776.2 link	c.841-238C>A	intron_variant	Intron 8 of 10		NP_001139248.1
FKBP5	NM_001145777.2 link	c.*6517C>A	downstream_gene_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9 link	c.841-238C>A		intron_variant	Intron 8 of 10	1	NM_004117.4	ENSP00000349811.3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149876

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

224620

Hom.:

AF XY:

0.00

AC XY:

AN XY:

114998

African (AFR)

AF:

0.00

AC:

AN:

6868

American (AMR)

AF:

0.00

AC:

AN:

8076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8178

East Asian (EAS)

AF:

0.00

AC:

AN:

19556

South Asian (SAS)

AF:

0.00

AC:

AN:

7114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1144

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

142570

Other (OTH)

AF:

0.00

AC:

AN:

14732

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72954

African (AFR)

AF:

0.00

AC:

AN:

40618

American (AMR)

AF:

0.00

AC:

AN:

15044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67642

Other (OTH)

AF:

0.00

AC:

AN:

2080

Alfa

AF:

0.00

Hom.:

56317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.20

(source)

DANN

Benign

0.62

PhyloP100

-0.96

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over