rs9380526

Variant names:

• chr6-35690550-C-T
• rs9380526
• ENST00000536438.5:c.-20+29778G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000536438.5(FKBP5):​c.-20+29778G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,938 control chromosomes in the GnomAD database, including 31,564 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 0.64 (31564 hom., cov: 30)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-20+29778G>A		intron_variant	Intron 2 of 11		NP_001139247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+29778G>A		intron_variant	Intron 2 of 11	1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97494 AN: 151820 Hom.: 31547 Cov.: 30

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.642 AC: 97548 AN: 151938 Hom.: 31564 Cov.: 30 AF XY: 0.647 AC XY: 48047 AN XY: 74294

African (AFR) AF: 0.552 AC: 22841 AN: 41378

American (AMR) AF: 0.641 AC: 9789 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3502 AN: 5164

South Asian (SAS) AF: 0.658 AC: 3161 AN: 4806

European-Finnish (FIN) AF: 0.764 AC: 8070 AN: 10562

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45485 AN: 67966

Other (OTH) AF: 0.640 AC: 1350 AN: 2110

Alfa AF: 0.657 Hom.: 42650

Bravo AF: 0.629

Asia WGS AF: 0.644 AC: 2236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.82
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9380526; hg19: chr6-35658327;