6-35669564-G-A

Position:

• chr6-35669564-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000357266.9(FKBP5):​c.-20+19240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 152,002 control chromosomes in the GnomAD database, including 8 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 0.0052 (8 hom., cov: 32)
• Consequence: FKBP5 ENST00000357266.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-20+19240C>T		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-26721C>T		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.-20+19168C>T		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.-20+19240C>T		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-20+19240C>T		intron_variant		1	NM_004117.4	ENSP00000349811	P1
FKBP5	ENST00000536438.5	c.-19-26721C>T		intron_variant		1		ENSP00000444810	P1
FKBP5	ENST00000539068.5	c.-20+19168C>T		intron_variant		1		ENSP00000441205	P1
FKBP5	ENST00000542713.1	c.-20+19240C>T		intron_variant		2		ENSP00000442340

Frequencies

GnomAD3 genomes AF: 0.00517 AC: 785 AN: 151884 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00671

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

GnomAD4 genome AF: 0.00516 AC: 784 AN: 152002 Hom.: 8 Cov.: 32 AF XY: 0.00493 AC XY: 366 AN XY: 74276

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00367

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00391 Hom.: 1

Bravo AF: 0.00597

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7762760; hg19: chr6-35637341;