6-35717713-G-A

Variant names:

• chr6-35717713-G-A
• rs2766533
• ENST00000536438.5:c.-20+2615C>T

Variant summary

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

The ENST00000536438.5(FKBP5):​c.-20+2615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,042 control chromosomes in the GnomAD database, including 13,236 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 0.41 (13236 hom., cov: 31)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 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+2615C>T		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+2615C>T		intron	N/A	ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61818 AN: 151924 Hom.: 13231 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.407 AC: 61839 AN: 152042 Hom.: 13236 Cov.: 31 AF XY: 0.408 AC XY: 30332 AN XY: 74316

African (AFR) AF: 0.278 AC: 11523 AN: 41464

American (AMR) AF: 0.381 AC: 5831 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1576 AN: 5168

South Asian (SAS) AF: 0.469 AC: 2260 AN: 4818

European-Finnish (FIN) AF: 0.527 AC: 5564 AN: 10564

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32531 AN: 67956

Other (OTH) AF: 0.396 AC: 837 AN: 2112

Alfa AF: 0.451 Hom.: 60218

Bravo AF: 0.389

Asia WGS AF: 0.418 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.63
DANN	Benign	0.79
PhyloP100		-0.38
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: rs2766533; hg19: chr6-35685490;