rs6912833

Positions:

• chr6-35649808-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004117.4(FKBP5):​c.-19-6965T>A 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 152,158 control chromosomes in the GnomAD database, including 45,119 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 0.77 (45119 hom., cov: 31)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-19-6965T>A		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-6965T>A		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.-19-6965T>A		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.-19-6965T>A		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-19-6965T>A		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-6965T>A		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-19-6965T>A		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-19-6965T>A		intron_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116515 AN: 152040 Hom.: 45061 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.767 AC: 116632 AN: 152158 Hom.: 45119 Cov.: 31 AF XY: 0.768 AC XY: 57150 AN XY: 74394

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.749

Alfa AF: 0.741 Hom.: 5201

Bravo AF: 0.769

Asia WGS AF: 0.733 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.41

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: rs6912833; hg19: chr6-35617585;