rs1591365

Variant names:

• chr6-35636330-G-A
• rs1591365
• NM_004117.4:c.250+684C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-35636330-G-A
• chr6-35636330-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004117.4(FKBP5):​c.250+684C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,100 control chromosomes in the GnomAD database, including 34,525 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 0.67 (34525 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.902
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.250+684C>T		intron_variant	Intron 3 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.250+684C>T		intron_variant	Intron 4 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.250+684C>T		intron_variant	Intron 3 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.250+684C>T		intron_variant	Intron 3 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.250+684C>T		intron_variant	Intron 3 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.250+684C>T		intron_variant	Intron 4 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.250+684C>T		intron_variant	Intron 3 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.250+684C>T		intron_variant	Intron 3 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102093 AN: 151982 Hom.: 34505 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.672 AC: 102152 AN: 152100 Hom.: 34525 Cov.: 32 AF XY: 0.677 AC XY: 50332 AN XY: 74378

African (AFR) AF: 0.586 AC: 24311 AN: 41476

American (AMR) AF: 0.674 AC: 10301 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3824 AN: 5186

South Asian (SAS) AF: 0.657 AC: 3165 AN: 4820

European-Finnish (FIN) AF: 0.803 AC: 8489 AN: 10576

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47297 AN: 67974

Other (OTH) AF: 0.653 AC: 1378 AN: 2110

Alfa AF: 0.688 Hom.: 7434

Bravo AF: 0.659

Asia WGS AF: 0.687 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.90
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: rs1591365; hg19: chr6-35604107;