rs4713921

Variant names:

• chr6-35714000-T-C
• rs4713921
• ENST00000536438.5:c.-20+6328A>G

Variant summary

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

The ENST00000536438.5(FKBP5):​c.-20+6328A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,698 control chromosomes in the GnomAD database, including 39,428 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 0.72 (39428 hom., cov: 29)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-20+6328A>G		intron_variant	Intron 2 of 11		NP_001139247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+6328A>G		intron_variant	Intron 2 of 11	1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109179 AN: 151580 Hom.: 39391 Cov.: 29

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.720 AC: 109273 AN: 151698 Hom.: 39428 Cov.: 29 AF XY: 0.720 AC XY: 53334 AN XY: 74088

African (AFR) AF: 0.770 AC: 31864 AN: 41366

American (AMR) AF: 0.700 AC: 10641 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2703 AN: 3468

East Asian (EAS) AF: 0.732 AC: 3723 AN: 5088

South Asian (SAS) AF: 0.659 AC: 3157 AN: 4792

European-Finnish (FIN) AF: 0.715 AC: 7526 AN: 10528

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47389 AN: 67932

Other (OTH) AF: 0.716 AC: 1509 AN: 2108

Alfa AF: 0.709 Hom.: 4738

Bravo AF: 0.722

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.024
DANN	Benign	0.46
PhyloP100		-2.2
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: rs4713921; hg19: chr6-35681777;