dbSNP rs755658: FKBP5:c.841-1672G>A (chr6-35581893-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.841-1672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 985,458 control chromosomes in the GnomAD database, including 4,311 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 0.066 ( 480 hom., cov: 32)

Exomes 𝑓: 0.095 ( 3831 hom. )

Consequence

FKBP5
NM_004117.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356

Publications

17 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4 link	c.841-1672G>A	intron_variant	Intron 8 of 10	ENST00000357266.9	NP_004108.1	Q13451-1Q2TA84
FKBP5	NM_001145777.2 link	c.*5083G>A	3_prime_UTR_variant	Exon 7 of 7		NP_001139249.1	Q13451-2
FKBP5	NM_001145775.3 link	c.841-1672G>A	intron_variant	Intron 9 of 11		NP_001139247.1	Q13451-1
FKBP5	NM_001145776.2 link	c.841-1672G>A	intron_variant	Intron 8 of 10		NP_001139248.1	Q13451-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9 link	c.841-1672G>A		intron_variant	Intron 8 of 10	1	NM_004117.4	ENSP00000349811.3		Q13451-1

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

10077

AN:

152132

Hom.:

479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.0636

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0418

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0919

Gnomad OTH

AF:

0.0612

GnomAD4 exome

AF:

0.0950

AC:

79147

AN:

833208

Hom.:

3831

Cov.:

AF XY:

0.0949

AC XY:

36513

AN XY:

384794

show subpopulations

African (AFR)

AF:

0.00962

AC:

152

AN:

15794

American (AMR)

AF:

0.125

AC:

123

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

108

AN:

5152

East Asian (EAS)

AF:

0.0705

AC:

256

AN:

3632

South Asian (SAS)

AF:

0.0621

AC:

1022

AN:

16462

European-Finnish (FIN)

AF:

0.0536

AC:

AN:

280

Middle Eastern (MID)

AF:

0.0327

AC:

AN:

1622

European-Non Finnish (NFE)

AF:

0.0986

AC:

75122

AN:

761982

Other (OTH)

AF:

0.0841

AC:

2296

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4311

8622

12932

17243

21554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3750

7500

11250

15000

18750

<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:

0.0662

AC:

10074

AN:

152250

Hom.:

480

Cov.:

AF XY:

0.0634

AC XY:

4720

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0184

AC:

765

AN:

41554

American (AMR)

AF:

0.116

AC:

1779

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3472

East Asian (EAS)

AF:

0.0634

AC:

328

AN:

5176

South Asian (SAS)

AF:

0.0605

AC:

292

AN:

4826

European-Finnish (FIN)

AF:

0.0418

AC:

444

AN:

10614

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0918

AC:

6244

AN:

68004

Other (OTH)

AF:

0.0606

AC:

128

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

473

946

1419

1892

2365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0864

Hom.:

460

Bravo

AF:

0.0710

Asia WGS

AF:

0.0590

AC:

204

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.52

(source)

DANN

Benign

0.52

PhyloP100

-0.36

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

Computational scores

Splicing

Publications

Other links and lift over