Genetic Variant FKBP5:c.-74A>G (chr6-35688786-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 ENST00000539068.5(FKBP5):c.-74A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 150,640 control chromosomes in the GnomAD database, including 45,766 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 0.78 ( 45753 hom., cov: 33)

Exomes 𝑓: 0.63 ( 13 hom. )

Consequence

FKBP5
ENST00000539068.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.567

Publications

4 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:

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=-0.64).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4 link	c.-20+18A>G	intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1	Q13451-1Q2TA84
FKBP5	NM_001145776.2 link	c.-74A>G	5_prime_UTR_variant	Exon 1 of 11		NP_001139248.1	Q13451-1
FKBP5	NM_001145775.3 link	c.-20+31542A>G	intron_variant	Intron 2 of 11		NP_001139247.1	Q13451-1
FKBP5	NM_001145777.2 link	c.-20+18A>G	intron_variant	Intron 1 of 6		NP_001139249.1	Q13451-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FKBP5	ENST00000539068.5 link	c.-74A>G	5_prime_UTR_variant	Exon 1 of 11	1		ENSP00000441205.1	Q13451-1
FKBP5	ENST00000357266.9 link	c.-20+18A>G	intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3	Q13451-1
FKBP5	ENST00000536438.5 link	c.-20+31542A>G	intron_variant	Intron 2 of 11	1		ENSP00000444810.1	Q13451-1
FKBP5	ENST00000542713.1 link	c.-20+18A>G	intron_variant	Intron 1 of 6	2		ENSP00000442340.1	Q13451-2

Frequencies

GnomAD3 genomes

AF:

0.775

AC:

116599

AN:

150470

Hom.:

45696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.903

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.781

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.712

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.629

AC:

AN:

Hom.:

Cov.:

AF XY:

0.583

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.607

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.775

AC:

116710

AN:

150578

Hom.:

45753

Cov.:

AF XY:

0.776

AC XY:

57097

AN XY:

73560

show subpopulations

African (AFR)

AF:

0.903

AC:

37341

AN:

41362

American (AMR)

AF:

0.735

AC:

11147

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.792

AC:

2732

AN:

3450

East Asian (EAS)

AF:

0.776

AC:

3975

AN:

5124

South Asian (SAS)

AF:

0.678

AC:

3275

AN:

4828

European-Finnish (FIN)

AF:

0.781

AC:

7833

AN:

10026

Middle Eastern (MID)

AF:

0.736

AC:

215

AN:

292

European-Non Finnish (NFE)

AF:

0.712

AC:

47931

AN:

67338

Other (OTH)

AF:

0.757

AC:

1583

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1342

2684

4025

5367

6709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.745

Hom.:

5161

Bravo

AF:

0.780

Asia WGS

AF:

0.720

AC:

2267

AN:

3156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-0.57

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=300/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over