6-35587406-C-A

Variant names:

• chr6-35587406-C-A
• rs992105
• NM_004117.4:c.757-289G>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.757-289G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,120 control chromosomes in the GnomAD database, including 53,101 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 0.83 (53101 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.68
• Publications: 21 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]

ENSG00000228559 (HGNC:58100):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.757-289G>T		intron_variant	Intron 7 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.757-289G>T		intron_variant	Intron 8 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.757-289G>T		intron_variant	Intron 7 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.666-289G>T		intron_variant	Intron 6 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.757-289G>T		intron_variant	Intron 7 of 10	1	NM_004117.4	ENSP00000349811.3

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126881 AN: 152002 Hom.: 53052 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.835 AC: 126986 AN: 152120 Hom.: 53101 Cov.: 32 AF XY: 0.835 AC XY: 62067 AN XY: 74372

African (AFR) AF: 0.837 AC: 34717 AN: 41460

American (AMR) AF: 0.841 AC: 12864 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2846 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4183 AN: 5178

South Asian (SAS) AF: 0.729 AC: 3511 AN: 4816

European-Finnish (FIN) AF: 0.867 AC: 9173 AN: 10578

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

European-Non Finnish (NFE) AF: 0.837 AC: 56941 AN: 68014

Other (OTH) AF: 0.803 AC: 1696 AN: 2112

Alfa AF: 0.838 Hom.: 50967

Bravo AF: 0.835

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.014
DANN	Benign	0.75
PhyloP100		-4.7
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: rs992105; hg19: chr6-35555183;