6-35678658-T-C

Variant names:

• chr6-35678658-T-C
• rs9470080
• NM_004117.4:c.-20+10146A>G

Variant summary

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

The NM_004117.4(FKBP5):​c.-20+10146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,058 control chromosomes in the GnomAD database, including 31,155 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 0.64 (31155 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 168 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=-0.74).
• 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.-20+10146A>G		intron	N/A	NP_004108.1	Q13451-1
	FKBP5	NM_001145775.3		c.-19-35815A>G		intron	N/A	NP_001139247.1	Q13451-1
	FKBP5	NM_001145776.2		c.-20+10074A>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.-20+10146A>G		intron	N/A	ENSP00000349811.3	Q13451-1
	FKBP5	ENST00000536438.5	TSL:1	c.-19-35815A>G		intron	N/A	ENSP00000444810.1	Q13451-1
	FKBP5	ENST00000539068.5	TSL:1	c.-20+10074A>G		intron	N/A	ENSP00000441205.1	Q13451-1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96783 AN: 151938 Hom.: 31139 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.637 AC: 96838 AN: 152058 Hom.: 31155 Cov.: 32 AF XY: 0.642 AC XY: 47715 AN XY: 74320

African (AFR) AF: 0.533 AC: 22120 AN: 41474

American (AMR) AF: 0.640 AC: 9778 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3503 AN: 5172

South Asian (SAS) AF: 0.662 AC: 3194 AN: 4822

European-Finnish (FIN) AF: 0.764 AC: 8065 AN: 10560

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45489 AN: 67982

Other (OTH) AF: 0.638 AC: 1345 AN: 2108

Alfa AF: 0.655 Hom.: 82641

Bravo AF: 0.624

Asia WGS AF: 0.653 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.63
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: rs9470080; hg19: chr6-35646435;