chr6-35690550-C-T

Position:

• chr6-35690550-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+29778G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,938 control chromosomes in the GnomAD database, including 31,564 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 0.64 (31564 hom., cov: 30)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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 (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_001145775.3	c.-20+29778G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+29778G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97494 AN: 151820 Hom.: 31547 Cov.: 30

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.642 AC: 97548 AN: 151938 Hom.: 31564 Cov.: 30 AF XY: 0.647 AC XY: 48047 AN XY: 74294

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.640

Alfa AF: 0.661 Hom.: 33274

Bravo AF: 0.629

Asia WGS AF: 0.644 AC: 2236 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	9.5
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: rs9380526; hg19: chr6-35658327;