chr6-35651777-G-A

Position:

• chr6-35651777-G-A

Variant summary

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

The NM_004117.4(FKBP5):​c.-19-8934C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 218,480 control chromosomes in the GnomAD database, including 200 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 0.043 (175 hom., cov: 32)
  • Exomes 𝑓: 0.023 (25 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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]

ENSG00000287458 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-19-8934C>T		intron_variant		ENST00000357266.9	NP_004108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-19-8934C>T		intron_variant		1	NM_004117.4	ENSP00000349811.3

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6478 AN: 152038 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0563

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.0229 AC: 1516 AN: 66324 Hom.: 25 Cov.: 4 AF XY: 0.0220 AC XY: 767 AN XY: 34802

Gnomad4 AFR exome AF: 0.0843

Gnomad4 AMR exome AF: 0.0516

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.0603

Gnomad4 SAS exome AF: 0.00636

Gnomad4 FIN exome AF: 0.0154

Gnomad4 NFE exome AF: 0.0217

Gnomad4 OTH exome AF: 0.0295

GnomAD4 genome AF: 0.0426 AC: 6484 AN: 152156 Hom.: 175 Cov.: 32 AF XY: 0.0423 AC XY: 3150 AN XY: 74400

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0563

Gnomad4 EAS AF: 0.0557

Gnomad4 SAS AF: 0.00747

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0284 Hom.: 97

Bravo AF: 0.0466

Asia WGS AF: 0.0300 AC: 105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.20

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: rs1475774; hg19: chr6-35619554;