rs7755289

Positions:

• chr6-35583636-T-A
• chr6-35583636-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004117.4(FKBP5):​c.840+3398A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 927,436 control chromosomes in the GnomAD database, including 10 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 0.0044 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (8 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_004117.4	c.840+3398A>T		intron_variant		ENST00000357266.9
LOC101929309	XR_242006.4	n.182-9394T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000357266.9	c.840+3398A>T		intron_variant		1	NM_004117.4	P1
FKBP5	ENST00000536438.5	c.840+3398A>T		intron_variant		1		P1
FKBP5	ENST00000539068.5	c.840+3398A>T		intron_variant		1		P1
FKBP5	ENST00000542713.1	c.*3340A>T		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 667 AN: 152164 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00419

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00402 AC: 3115 AN: 775154 Hom.: 8 Cov.: 11 AF XY: 0.00396 AC XY: 1422 AN XY: 359432

Gnomad4 AFR exome AF: 0.00321

Gnomad4 AMR exome AF: 0.00434

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.00179

Gnomad4 SAS exome AF: 0.00236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00398

Gnomad4 OTH exome AF: 0.00465

GnomAD4 genome AF: 0.00437 AC: 666 AN: 152282 Hom.: 2 Cov.: 32 AF XY: 0.00447 AC XY: 333 AN XY: 74458

Gnomad4 AFR AF: 0.00313

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00418

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00365 Hom.: 0

Bravo AF: 0.00580

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.54

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: rs7755289; hg19: chr6-35551413;