rs9470065

Positions:

• chr6-35582376-G-A

Variant summary

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

The NM_001145777.2(FKBP5):​c.*4600C>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 0.00618 in 822,288 control chromosomes in the GnomAD database, including 208 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 0.024 (144 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (64 hom.)
• Consequence: FKBP5 NM_001145777.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.841-2155C>T		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145777.2	c.*4600C>T		3_prime_UTR_variant	7/7		NP_001139249.1
FKBP5	NM_001145775.3	c.841-2155C>T		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.841-2155C>T		intron_variant			NP_001139248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.841-2155C>T		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.841-2155C>T		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.841-2155C>T		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713	c.*4600C>T		3_prime_UTR_variant	7/7	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3686 AN: 152118 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.00207 AC: 1388 AN: 670052 Hom.: 64 Cov.: 9 AF XY: 0.00183 AC XY: 571 AN XY: 312098

Gnomad4 AFR exome AF: 0.0963

Gnomad4 AMR exome AF: 0.00754

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000153

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000116

Gnomad4 OTH exome AF: 0.00487

GnomAD4 genome AF: 0.0242 AC: 3691 AN: 152236 Hom.: 144 Cov.: 32 AF XY: 0.0234 AC XY: 1742 AN XY: 74442

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0190 Hom.: 12

Bravo AF: 0.0287

Asia WGS AF: 0.00346 AC: 12 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	1.1
DANN	Benign	0.30

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: rs9470065; hg19: chr6-35550153;