rs9380525

Variant names:

• chr6-35665261-G-C
• rs9380525
• NM_004117.4:c.-19-22418C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-35665261-G-C
• chr6-35665261-G-A

Variant summary

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

The NM_004117.4(FKBP5):​c.-19-22418C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,294 control chromosomes in the GnomAD database, including 31,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars).

• Frequency: Genomes: 𝑓 0.64 (31356 hom., cov: 28)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: -0.257
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004117.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_004117.4	MANE Select	c.-19-22418C>G		intron	N/A	NP_004108.1	Q13451-1
	FKBP5	NM_001145775.3		c.-19-22418C>G		intron	N/A	NP_001139247.1	Q13451-1
	FKBP5	NM_001145776.2		c.-19-22418C>G		intron	N/A	NP_001139248.1	Q13451-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.-19-22418C>G		intron	N/A	ENSP00000349811.3	Q13451-1
	FKBP5	ENST00000536438.5	TSL:1	c.-19-22418C>G		intron	N/A	ENSP00000444810.1	Q13451-1
	FKBP5	ENST00000539068.5	TSL:1	c.-19-22418C>G		intron	N/A	ENSP00000441205.1	Q13451-1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 96989 AN: 151202 Hom.: 31340 Cov.: 28

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.641 AC: 97044 AN: 151294 Hom.: 31356 Cov.: 28 AF XY: 0.646 AC XY: 47761 AN XY: 73886

African (AFR) AF: 0.548 AC: 22525 AN: 41132

American (AMR) AF: 0.644 AC: 9776 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2523 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3480 AN: 5132

South Asian (SAS) AF: 0.663 AC: 3176 AN: 4788

European-Finnish (FIN) AF: 0.763 AC: 7931 AN: 10390

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.670 AC: 45463 AN: 67896

Other (OTH) AF: 0.645 AC: 1351 AN: 2096

Alfa AF: 0.564 Hom.: 1630

Bravo AF: 0.628

Asia WGS AF: 0.656 AC: 2279 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely risk allele

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Susceptibility to severe depressive disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.61
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9380525; hg19: chr6-35633038;