6-35639794-T-C

Position:

• chr6-35639794-T-C

Variant summary

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

The NM_004117.4(FKBP5):​c.106-2636A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,130 control chromosomes in the GnomAD database, including 34,608 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 0.67 (34608 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: -0.0870

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 6-35639794-T-C is Pathogenic according to our data. Variant chr6-35639794-T-C is described in ClinVar as [Likely_risk_allele]. Clinvar id is 1712509.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=-0.89). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.106-2636A>G		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.106-2636A>G		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.106-2636A>G		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.106-2636A>G		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.106-2636A>G		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.106-2636A>G		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.106-2636A>G		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.106-2636A>G		intron_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102235 AN: 152012 Hom.: 34588 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.672 AC: 102294 AN: 152130 Hom.: 34608 Cov.: 32 AF XY: 0.677 AC XY: 50377 AN XY: 74368

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.655

Alfa AF: 0.686 Hom.: 17078

Bravo AF: 0.660

Asia WGS AF: 0.686 AC: 2381 AN: 3476

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Post-traumatic stress disorder Pathogenic:1

Likely risk allele, no assertion criteria provided

research

Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.70

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: rs1360780; hg19: chr6-35607571;