rs9394314

Positions:

• chr6-35715282-G-A

Variant summary

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

The NM_001145775.3(FKBP5):​c.-20+5046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,042 control chromosomes in the GnomAD database, including 40,564 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 0.73 (40564 hom., cov: 32)
• Consequence: FKBP5 NM_001145775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-20+5046C>T		intron_variant			NP_001139247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+5046C>T		intron_variant		1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110776 AN: 151924 Hom.: 40526 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.729 AC: 110871 AN: 152042 Hom.: 40564 Cov.: 32 AF XY: 0.729 AC XY: 54156 AN XY: 74322

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.722

Alfa AF: 0.706 Hom.: 65150

Bravo AF: 0.732

Asia WGS AF: 0.699 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9394314; hg19: chr6-35683059;