rs4713916

Variant names:

• chr6-35702206-A-G
• rs4713916
• ENST00000536438.5:c.-20+18122T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-35702206-A-G
• chr6-35702206-A-C
• chr6-35702206-A-T

Variant summary

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

The NM_001145775.3(FKBP5):​c.-20+18122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 151,870 control chromosomes in the GnomAD database, including 45,188 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 0.77 (45188 hom., cov: 29)
• Consequence: FKBP5 NM_001145775.3 intron
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: -0.495
• Publications: 97 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 = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145775.3. 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_001145775.3		c.-20+18122T>C		intron	N/A	NP_001139247.1	Q13451-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000536438.5	TSL:1	c.-20+18122T>C		intron	N/A	ENSP00000444810.1	Q13451-1
	FKBP5	ENST00000893094.1		c.-20+18122T>C		intron	N/A	ENSP00000563153.1
	FKBP5	ENST00000893095.1		c.-78-17721T>C		intron	N/A	ENSP00000563154.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116353 AN: 151754 Hom.: 45129 Cov.: 29

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.767 AC: 116470 AN: 151870 Hom.: 45188 Cov.: 29 AF XY: 0.766 AC XY: 56850 AN XY: 74198

African (AFR) AF: 0.897 AC: 37157 AN: 41438

American (AMR) AF: 0.732 AC: 11162 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2757 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3970 AN: 5152

South Asian (SAS) AF: 0.671 AC: 3222 AN: 4800

European-Finnish (FIN) AF: 0.732 AC: 7706 AN: 10526

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48010 AN: 67924

Other (OTH) AF: 0.755 AC: 1592 AN: 2110

Alfa AF: 0.749 Hom.: 31638

Bravo AF: 0.774

Asia WGS AF: 0.714 AC: 2481 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	-0.94
CADD	Benign	0.26
DANN	Benign	0.67
PhyloP100		-0.49
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: rs4713916; hg19: chr6-35669983;