6-35717937-G-T

Variant names:

• chr6-35717937-G-T
• rs2766534
• ENST00000536438.5:c.-20+2391C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000536438.5(FKBP5):​c.-20+2391C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,016 control chromosomes in the GnomAD database, including 41,573 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 0.74 (41573 hom., cov: 32)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000536438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_001145775.3		c.-20+2391C>A		intron	N/A	NP_001139247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000536438.5	TSL:1	c.-20+2391C>A		intron	N/A	ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111891 AN: 151898 Hom.: 41522 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.766

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.737 AC: 111998 AN: 152016 Hom.: 41573 Cov.: 32 AF XY: 0.735 AC XY: 54615 AN XY: 74310

African (AFR) AF: 0.641 AC: 26575 AN: 41474

American (AMR) AF: 0.771 AC: 11777 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2500 AN: 3462

East Asian (EAS) AF: 0.593 AC: 3051 AN: 5148

South Asian (SAS) AF: 0.743 AC: 3576 AN: 4816

European-Finnish (FIN) AF: 0.807 AC: 8537 AN: 10578

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53400 AN: 67950

Other (OTH) AF: 0.768 AC: 1623 AN: 2112

Alfa AF: 0.773 Hom.: 44407

Bravo AF: 0.733

Asia WGS AF: 0.738 AC: 2566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.083
DANN	Benign	0.82
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2766534; hg19: chr6-35685714;