6-35694042-C-T

Variant names:

• chr6-35694042-C-T
• rs7759392
• ENST00000536438.5:c.-20+26286G>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+26286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 151,854 control chromosomes in the GnomAD database, including 45,705 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 (45705 hom., cov: 30)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-20+26286G>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+26286G>A		intron_variant	Intron 2 of 11	1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117129 AN: 151734 Hom.: 45650 Cov.: 30

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.742

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: 0.772 AC: 117242 AN: 151854 Hom.: 45705 Cov.: 30 AF XY: 0.773 AC XY: 57379 AN XY: 74204

African (AFR) AF: 0.894 AC: 37052 AN: 41454

American (AMR) AF: 0.729 AC: 11101 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2745 AN: 3468

East Asian (EAS) AF: 0.779 AC: 4016 AN: 5156

South Asian (SAS) AF: 0.674 AC: 3234 AN: 4798

European-Finnish (FIN) AF: 0.783 AC: 8251 AN: 10538

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.712 AC: 48367 AN: 67912

Other (OTH) AF: 0.754 AC: 1584 AN: 2100

Alfa AF: 0.744 Hom.: 5233

Bravo AF: 0.774

Asia WGS AF: 0.722 AC: 2506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.15
PhyloP100		-0.48
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: rs7759392; hg19: chr6-35661819;