6-35702206-A-G

Position:

• chr6-35702206-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The NM_001145775.3(FKBP5):​c.-20+18122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 151,870 control chromosomes in the GnomAD database, including 45,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars).

• Frequency: Genomes: 𝑓 0.77 (45188 hom., cov: 29)
• Consequence: FKBP5 NM_001145775.3 intron
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: -0.495

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 -8 ACMG points.

• PP5: Variant 6-35702206-A-G is Pathogenic according to our data. Variant chr6-35702206-A-G is described in ClinVar as [Likely_risk_allele]. Clinvar id is 1702943.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-20+18122T>C		intron_variant			NP_001139247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+18122T>C		intron_variant		1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116353 AN: 151754 Hom.: 45129 Cov.: 29

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.767 AC: 116470 AN: 151870 Hom.: 45188 Cov.: 29 AF XY: 0.766 AC XY: 56850 AN XY: 74198

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.755

Alfa AF: 0.697 Hom.: 6649

Bravo AF: 0.774

Asia WGS AF: 0.714 AC: 2481 AN: 3478

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Susceptibility to severe depressive disorder Pathogenic:1

Likely risk allele, no assertion criteria provided

case-control

Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology

Jul 01, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4713916; hg19: chr6-35669983;