dbSNP rs7755289: FKBP5:c.840+3398A>T (chr6-35583636-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004117.4(FKBP5):c.840+3398A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 927,436 control chromosomes in the GnomAD database, including 10 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 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 8 hom. )

Consequence

FKBP5
NM_004117.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

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:

ENSG00000228559 (HGNC:58100):

ENSG00000228559 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4 link	c.840+3398A>T	intron_variant	Intron 8 of 10	ENST00000357266.9	NP_004108.1	Q13451-1Q2TA84
FKBP5	NM_001145777.2 link	c.*3340A>T	3_prime_UTR_variant	Exon 7 of 7		NP_001139249.1	Q13451-2
FKBP5	NM_001145775.3 link	c.840+3398A>T	intron_variant	Intron 9 of 11		NP_001139247.1	Q13451-1
FKBP5	NM_001145776.2 link	c.840+3398A>T	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.840+3398A>T		intron_variant	Intron 8 of 10	1	NM_004117.4	ENSP00000349811.3		Q13451-1

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

667

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00402

AC:

3115

AN:

775154

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

1422

AN XY:

359432

show subpopulations

African (AFR)

AF:

0.00321

AC:

AN:

14642

American (AMR)

AF:

0.00434

AC:

AN:

922

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

4762

East Asian (EAS)

AF:

0.00179

AC:

AN:

3348

South Asian (SAS)

AF:

0.00236

AC:

AN:

15270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

268

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

1516

European-Non Finnish (NFE)

AF:

0.00398

AC:

2823

AN:

709042

Other (OTH)

AF:

0.00465

AC:

118

AN:

25384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

142

284

427

569

711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<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:

0.00437

AC:

666

AN:

152282

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00313

AC:

130

AN:

41568

American (AMR)

AF:

0.0105

AC:

161

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.00208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00418

AC:

284

AN:

68008

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00365

Hom.:

Bravo

AF:

0.00580

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.41

(source)

DANN

Benign

0.54

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism

(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