rs7763535

chr6-35694329-C-Achr6-35694329-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000536438.5(FKBP5):c.-20+25999G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 151,828 control chromosomes in the GnomAD database, including 45,865 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 0.77 (45865 hom., cov: 29)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_001145775.3	c.-20+25999G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+25999G>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117250 AN: 151710 Hom.: 45805 Cov.: 29

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.773 AC: 117368 AN: 151828 Hom.: 45865 Cov.: 29 AF XY: 0.774 AC XY: 57432 AN XY: 74172

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.754

Alfa AF: 0.649 Hom.: 1783

Bravo AF: 0.777

Asia WGS AF: 0.722 AC: 2507 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	2.6
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7763535; hg19: chr6-35662106;