6-35599305-A-G

Position:

• chr6-35599305-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004117.4(FKBP5):​c.509-1901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,050 control chromosomes in the GnomAD database, including 32,832 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 0.65 (32832 hom., cov: 31)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.509-1901T>C		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.509-1901T>C		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.509-1901T>C		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.509-1901T>C		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.509-1901T>C		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.509-1901T>C		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.509-1901T>C		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.509-1901T>C		intron_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99127 AN: 151932 Hom.: 32809 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.652 AC: 99188 AN: 152050 Hom.: 32832 Cov.: 31 AF XY: 0.658 AC XY: 48892 AN XY: 74348

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.630

Alfa AF: 0.687 Hom.: 33521

Bravo AF: 0.634

Asia WGS AF: 0.725 AC: 2288 AN: 3158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.56

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: rs9296158; hg19: chr6-35567082;