6-35720842-T-C

Position:

• chr6-35720842-T-C

Variant summary

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

The ENST00000536438.5(FKBP5):​c.-240-294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,146 control chromosomes in the GnomAD database, including 4,871 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 0.24 (4871 hom., cov: 32)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_001145775.3	c.-240-294A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000536438.5	c.-240-294A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36603 AN: 152028 Hom.: 4864 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.241 AC: 36628 AN: 152146 Hom.: 4871 Cov.: 32 AF XY: 0.243 AC XY: 18078 AN XY: 74386

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.256

Alfa AF: 0.274 Hom.: 6302

Bravo AF: 0.234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.39
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2817032; hg19: chr6-35688619;