rs9394314

Variant names:

• chr6-35715282-G-A
• rs9394314
• ENST00000536438.5:c.-20+5046C>T

Variant summary

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

The ENST00000536438.5(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 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• 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=-0.93).
• 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 rank	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-20+5046C>T		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+5046C>T		intron_variant	Intron 2 of 11	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

African (AFR) AF: 0.797 AC: 33046 AN: 41466

American (AMR) AF: 0.708 AC: 10818 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2703 AN: 3468

East Asian (EAS) AF: 0.744 AC: 3845 AN: 5168

South Asian (SAS) AF: 0.658 AC: 3173 AN: 4822

European-Finnish (FIN) AF: 0.717 AC: 7566 AN: 10556

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47433 AN: 67980

Other (OTH) AF: 0.722 AC: 1524 AN: 2110

Alfa AF: 0.708 Hom.: 155789

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
PhyloP100		-0.31
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: rs9394314; hg19: chr6-35683059;