rs2766533

Positions:

• chr6-35717713-G-A
• chr6-35717713-G-C

Variant summary

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

The ENST00000536438.5(FKBP5):​c.-20+2615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,042 control chromosomes in the GnomAD database, including 13,236 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 0.41 (13236 hom., cov: 31)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_001145775.3	c.-20+2615C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+2615C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61818 AN: 151924 Hom.: 13231 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.407 AC: 61839 AN: 152042 Hom.: 13236 Cov.: 31 AF XY: 0.408 AC XY: 30332 AN XY: 74316

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.396

Alfa AF: 0.456 Hom.: 26483

Bravo AF: 0.389

Asia WGS AF: 0.418 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.63
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2766533; hg19: chr6-35685490;