dbSNP rs2143404: FKBP5:c.-19-61A>T (chr6-35642904-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004117.4(FKBP5):c.-19-61A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000593 in 1,197,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

FKBP5
NM_004117.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Publications

10 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.-19-61A>T	intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1	Q13451-1Q2TA84
FKBP5	NM_001145775.3 link	c.-19-61A>T	intron_variant	Intron 2 of 11		NP_001139247.1	Q13451-1
FKBP5	NM_001145776.2 link	c.-19-61A>T	intron_variant	Intron 1 of 10		NP_001139248.1	Q13451-1
FKBP5	NM_001145777.2 link	c.-19-61A>T	intron_variant	Intron 1 of 6		NP_001139249.1	Q13451-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FKBP5	ENST00000357266.9 link	c.-19-61A>T	intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3	Q13451-1
FKBP5	ENST00000536438.5 link	c.-19-61A>T	intron_variant	Intron 2 of 11	1		ENSP00000444810.1	Q13451-1
FKBP5	ENST00000539068.5 link	c.-19-61A>T	intron_variant	Intron 1 of 10	1		ENSP00000441205.1	Q13451-1
FKBP5	ENST00000542713.1 link	c.-19-61A>T	intron_variant	Intron 1 of 6	2		ENSP00000442340.1	Q13451-2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000584

AC:

AN:

1045086

Hom.:

AF XY:

0.0000560

AC XY:

AN XY:

535762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24674

American (AMR)

AF:

0.00

AC:

AN:

39036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21350

East Asian (EAS)

AF:

0.00

AC:

AN:

37170

South Asian (SAS)

AF:

0.00

AC:

AN:

72432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4688

European-Non Finnish (NFE)

AF:

0.0000793

AC:

AN:

756500

Other (OTH)

AF:

0.0000216

AC:

AN:

46340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.0000658

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.0000655

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

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:

0.00

Hom.:

4220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.60

PhyloP100

-1.7

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