rs755658

Positions:

• chr6-35581893-C-T

Variant summary

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

The ENST00000357266.9(FKBP5):​c.841-1672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 985,458 control chromosomes in the GnomAD database, including 4,311 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 0.066 (480 hom., cov: 32)
  • Exomes 𝑓: 0.095 (3831 hom.)
• Consequence: FKBP5 ENST00000357266.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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]

LOC101929309 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.841-1672G>A		intron_variant		ENST00000357266.9	NP_004108.1
LOC101929309	XR_242006.4	n.182-11137C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.841-1672G>A		intron_variant		1	NM_004117.4	ENSP00000349811	P1
FKBP5	ENST00000536438.5	c.841-1672G>A		intron_variant		1		ENSP00000444810	P1
FKBP5	ENST00000539068.5	c.841-1672G>A		intron_variant		1		ENSP00000441205	P1
FKBP5	ENST00000542713.1	c.*5083G>A		3_prime_UTR_variant	7/7	2		ENSP00000442340

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10077 AN: 152132 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0636

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0950 AC: 79147 AN: 833208 Hom.: 3831 Cov.: 33 AF XY: 0.0949 AC XY: 36513 AN XY: 384794

Gnomad4 AFR exome AF: 0.00962

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.0705

Gnomad4 SAS exome AF: 0.0621

Gnomad4 FIN exome AF: 0.0536

Gnomad4 NFE exome AF: 0.0986

Gnomad4 OTH exome AF: 0.0841

GnomAD4 genome AF: 0.0662 AC: 10074 AN: 152250 Hom.: 480 Cov.: 32 AF XY: 0.0634 AC XY: 4720 AN XY: 74436

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.0634

Gnomad4 SAS AF: 0.0605

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.0606

Alfa AF: 0.0857 Hom.: 247

Bravo AF: 0.0710

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.52

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: rs755658; hg19: chr6-35549670;