dbSNP rs3734257: FKBP5:c.841-1828C>T (chr6-35582049-G-A) – 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.841-1828C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 985,628 control chromosomes in the GnomAD database, including 1 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 0.00033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

FKBP5
NM_004117.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.184

Publications

1 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:

Genome browser will be placed here

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=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4 link	c.841-1828C>T	intron_variant	Intron 8 of 10	ENST00000357266.9	NP_004108.1	Q13451-1Q2TA84
FKBP5	NM_001145777.2 link	c.*4927C>T	3_prime_UTR_variant	Exon 7 of 7		NP_001139249.1	Q13451-2
FKBP5	NM_001145775.3 link	c.841-1828C>T	intron_variant	Intron 9 of 11		NP_001139247.1	Q13451-1
FKBP5	NM_001145776.2 link	c.841-1828C>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.841-1828C>T		intron_variant	Intron 8 of 10	1	NM_004117.4	ENSP00000349811.3		Q13451-1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00926

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.0000492

AC:

AN:

833334

Hom.:

Cov.:

AF XY:

0.0000338

AC XY:

AN XY:

384896

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

15794

American (AMR)

AF:

0.00

AC:

AN:

988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5154

East Asian (EAS)

AF:

0.00797

AC:

AN:

3638

South Asian (SAS)

AF:

0.0000607

AC:

AN:

16462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

762084

Other (OTH)

AF:

0.000366

AC:

AN:

27312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000328

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00928

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000252

Hom.:

Bravo

AF:

0.000412

Asia WGS

AF:

0.00231

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

1.3

(source)

DANN

Benign

0.40

PhyloP100

0.18

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