rs992105

Positions:

• chr6-35587406-C-A
• chr6-35587406-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC101929309 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.757-289G>T		intron_variant		ENST00000357266.9	NP_004108.1
LOC101929309	XR_242006.4	n.182-5624C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.757-289G>T		intron_variant		1	NM_004117.4	ENSP00000349811	P1
FKBP5	ENST00000536438.5	c.757-289G>T		intron_variant		1		ENSP00000444810	P1
FKBP5	ENST00000539068.5	c.757-289G>T		intron_variant		1		ENSP00000441205	P1
FKBP5	ENST00000542713.1	c.666-289G>T		intron_variant		2		ENSP00000442340

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

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.803

Alfa AF: 0.835 Hom.: 31071

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs992105; hg19: chr6-35555183;