6-35601504-A-G

Variant names:

• chr6-35601504-A-G
• rs4713899
• NM_004117.4:c.509-4100T>C

Variant summary

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

The NM_004117.4(FKBP5):​c.509-4100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,198 control chromosomes in the GnomAD database, including 55,027 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 0.85 (55027 hom., cov: 31)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 15 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_004117.4	MANE Select	c.509-4100T>C		intron	N/A	NP_004108.1
	FKBP5	NM_001145775.3		c.509-4100T>C		intron	N/A	NP_001139247.1
	FKBP5	NM_001145776.2		c.509-4100T>C		intron	N/A	NP_001139248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.509-4100T>C		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.509-4100T>C		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.509-4100T>C		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129126 AN: 152080 Hom.: 54975 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.849 AC: 129236 AN: 152198 Hom.: 55027 Cov.: 31 AF XY: 0.848 AC XY: 63072 AN XY: 74394

African (AFR) AF: 0.897 AC: 37241 AN: 41522

American (AMR) AF: 0.845 AC: 12925 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2809 AN: 3468

East Asian (EAS) AF: 0.805 AC: 4161 AN: 5172

South Asian (SAS) AF: 0.727 AC: 3509 AN: 4826

European-Finnish (FIN) AF: 0.863 AC: 9143 AN: 10592

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56769 AN: 68010

Other (OTH) AF: 0.809 AC: 1712 AN: 2116

Alfa AF: 0.845 Hom.: 41106

Bravo AF: 0.851

Asia WGS AF: 0.770 AC: 2676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.51
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: rs4713899; hg19: chr6-35569281;