6-35678658-T-C

Position:

• chr6-35678658-T-C

Variant summary

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

The NM_004117.4(FKBP5):​c.-20+10146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,058 control chromosomes in the GnomAD database, including 31,155 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 (31155 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630

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=-0.74).
• 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	Protein	UniProt
FKBP5	NM_004117.4	c.-20+10146A>G		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-35815A>G		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.-20+10074A>G		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.-20+10146A>G		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-20+10146A>G		intron_variant		1	NM_004117.4	ENSP00000349811	P1
FKBP5	ENST00000536438.5	c.-19-35815A>G		intron_variant		1		ENSP00000444810	P1
FKBP5	ENST00000539068.5	c.-20+10074A>G		intron_variant		1		ENSP00000441205	P1
FKBP5	ENST00000542713.1	c.-20+10146A>G		intron_variant		2		ENSP00000442340

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96783 AN: 151938 Hom.: 31139 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.637 AC: 96838 AN: 152058 Hom.: 31155 Cov.: 32 AF XY: 0.642 AC XY: 47715 AN XY: 74320

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.638

Alfa AF: 0.664 Hom.: 53461

Bravo AF: 0.624

Asia WGS AF: 0.653 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.85

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: rs9470080; hg19: chr6-35646435;