chr6-35574268-C-A

Position:

• chr6-35574268-C-A

Variant summary

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

The ENST00000357266.9(FKBP5):​c.*1567G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 152,050 control chromosomes in the GnomAD database, including 787 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 0.072 (787 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: FKBP5 ENST00000357266.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.*1567G>T		3_prime_UTR_variant	11/11	ENST00000357266.9	NP_004108.1
LOC101929309	XR_242006.4	n.182-18762C>A		intron_variant, non_coding_transcript_variant
FKBP5	NM_001145775.3	c.*1567G>T		3_prime_UTR_variant	12/12		NP_001139247.1
FKBP5	NM_001145776.2	c.*1567G>T		3_prime_UTR_variant	11/11		NP_001139248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.*1567G>T		3_prime_UTR_variant	11/11	1	NM_004117.4	ENSP00000349811	P1
FKBP5	ENST00000536438.5	c.*1567G>T		3_prime_UTR_variant	12/12	1		ENSP00000444810	P1
FKBP5	ENST00000539068.5	c.*1567G>T		3_prime_UTR_variant	11/11	1		ENSP00000441205	P1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10929 AN: 151932 Hom.: 783 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00583

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0694

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0721 AC: 10959 AN: 152050 Hom.: 787 Cov.: 33 AF XY: 0.0706 AC XY: 5248 AN XY: 74332

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00562

Gnomad4 FIN AF: 0.0134

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0430 Hom.: 74

Bravo AF: 0.0795

Asia WGS AF: 0.0140 AC: 47 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs41270080; hg19: chr6-35542045;