dbSNP rs13215797: FKBP5:c.-20+150G>A (chr6-35688654-C-T) – 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.-20+150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 150,722 control chromosomes in the GnomAD database, including 1,284 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 0.11 ( 1282 hom., cov: 33)

Exomes 𝑓: 0.34 ( 2 hom. )

Consequence

FKBP5
NM_004117.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.465

Publications

5 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:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FKBP5	NM_004117.4 link	c.-20+150G>A	intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3 link	c.-20+31674G>A	intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2 link	c.-20+78G>A	intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2 link	c.-20+150G>A	intron_variant	Intron 1 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
FKBP5	ENST00000357266.9 link	c.-20+150G>A	intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5 link	c.-20+31674G>A	intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5 link	c.-20+78G>A	intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1 link	c.-20+150G>A	intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16762

AN:

150582

Hom.:

1277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.155

GnomAD4 exome

AF:

0.344

AC:

AN:

Hom.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.321

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16783

AN:

150690

Hom.:

1282

Cov.:

AF XY:

0.113

AC XY:

8301

AN XY:

73618

show subpopulations

African (AFR)

AF:

0.0238

AC:

985

AN:

41384

American (AMR)

AF:

0.219

AC:

3315

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

529

AN:

3454

East Asian (EAS)

AF:

0.206

AC:

1047

AN:

5092

South Asian (SAS)

AF:

0.121

AC:

583

AN:

4828

European-Finnish (FIN)

AF:

0.128

AC:

1287

AN:

10050

Middle Eastern (MID)

AF:

0.188

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.128

AC:

8634

AN:

67446

Other (OTH)

AF:

0.157

AC:

327

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

748

1496

2245

2993

3741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.117

Hom.:

166

Bravo

AF:

0.119

Asia WGS

AF:

0.180

AC:

594

AN:

3310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-0.47

PromoterAI

-0.092

Neutral

(source)

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)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over