6-35700083-T-C

Variant names:

• chr6-35700083-T-C
• rs943297
• ENST00000536438.5:c.-20+20245A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000536438.5(FKBP5):​c.-20+20245A>G 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 152,044 control chromosomes in the GnomAD database, including 45,239 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 (45239 hom., cov: 30)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-20+20245A>G		intron_variant	Intron 2 of 11		NP_001139247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000536438.5	c.-20+20245A>G		intron_variant	Intron 2 of 11	1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116477 AN: 151926 Hom.: 45179 Cov.: 30

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.767 AC: 116596 AN: 152044 Hom.: 45239 Cov.: 30 AF XY: 0.766 AC XY: 56947 AN XY: 74302

African (AFR) AF: 0.897 AC: 37227 AN: 41518

American (AMR) AF: 0.732 AC: 11174 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2754 AN: 3468

East Asian (EAS) AF: 0.770 AC: 3967 AN: 5150

South Asian (SAS) AF: 0.670 AC: 3219 AN: 4804

European-Finnish (FIN) AF: 0.733 AC: 7750 AN: 10566

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48021 AN: 67962

Other (OTH) AF: 0.756 AC: 1590 AN: 2104

Alfa AF: 0.756 Hom.: 7676

Bravo AF: 0.774

Asia WGS AF: 0.715 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.94
DANN	Benign	0.32
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs943297; hg19: chr6-35667860;