rs9380524

chr6-35621293-C-Achr6-35621293-C-T

Variant summary

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

The NM_004117.4(FKBP5):c.251-1019G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 152,100 control chromosomes in the GnomAD database, including 983 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 0.094 (983 hom., cov: 31)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_004117.4	c.251-1019G>T		intron_variant		ENST00000357266.9
FKBP5	NM_001145775.3	c.251-1019G>T		intron_variant
FKBP5	NM_001145776.2	c.251-1019G>T		intron_variant
FKBP5	NM_001145777.2	c.251-1019G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000357266.9	c.251-1019G>T		intron_variant		1	NM_004117.4	P1
FKBP5	ENST00000536438.5	c.251-1019G>T		intron_variant		1		P1
FKBP5	ENST00000539068.5	c.251-1019G>T		intron_variant		1		P1
FKBP5	ENST00000542713.1	c.251-1019G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14348 AN: 151982 Hom.: 983 Cov.: 31

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0676

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

GnomAD4 genome AF: 0.0943 AC: 14344 AN: 152100 Hom.: 983 Cov.: 31 AF XY: 0.100 AC XY: 7435 AN XY: 74338

Gnomad4 AFR AF: 0.0254

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0674

Alfa AF: 0.0960 Hom.: 813

Bravo AF: 0.0875

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.72
Dann	Benign	0.70

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: rs9380524; hg19: chr6-35589070;