rs4713907

Variant names:

• chr6-35675298-G-A
• rs4713907
• NM_004117.4:c.-20+13506C>T

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+13506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 152,188 control chromosomes in the GnomAD database, including 177 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 0.043 (177 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 4 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-20+13506C>T		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-32455C>T		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-20+13434C>T		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-20+13506C>T		intron_variant	Intron 1 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-20+13506C>T		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-32455C>T		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-20+13434C>T		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-20+13506C>T		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6490 AN: 152070 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0427 AC: 6496 AN: 152188 Hom.: 177 Cov.: 32 AF XY: 0.0423 AC XY: 3148 AN XY: 74424

African (AFR) AF: 0.0796 AC: 3305 AN: 41516

American (AMR) AF: 0.0486 AC: 744 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3470

East Asian (EAS) AF: 0.0557 AC: 288 AN: 5174

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4828

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10594

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1638 AN: 67998

Other (OTH) AF: 0.0422 AC: 89 AN: 2110

Alfa AF: 0.0338 Hom.: 13

Bravo AF: 0.0467

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.41
DANN	Benign	0.87
PhyloP100		-1.9
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: rs4713907; hg19: chr6-35643075;