6-35703388-A-G

Variant names:

• chr6-35703388-A-G
• rs2395635
• ENST00000536438.5:c.-20+16940T>C

Variant summary

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

The ENST00000536438.5(FKBP5):​c.-20+16940T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 151,984 control chromosomes in the GnomAD database, including 44,936 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 0.76 (44936 hom., cov: 30)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 6 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000536438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_001145775.3		c.-20+16940T>C		intron	N/A	NP_001139247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000536438.5	TSL:1	c.-20+16940T>C		intron	N/A	ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116147 AN: 151866 Hom.: 44886 Cov.: 30

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.765 AC: 116255 AN: 151984 Hom.: 44936 Cov.: 30 AF XY: 0.765 AC XY: 56780 AN XY: 74268

African (AFR) AF: 0.888 AC: 36813 AN: 41464

American (AMR) AF: 0.732 AC: 11153 AN: 15242

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

East Asian (EAS) AF: 0.772 AC: 3995 AN: 5178

South Asian (SAS) AF: 0.673 AC: 3236 AN: 4808

European-Finnish (FIN) AF: 0.732 AC: 7713 AN: 10534

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

European-Non Finnish (NFE) AF: 0.708 AC: 48104 AN: 67970

Other (OTH) AF: 0.754 AC: 1593 AN: 2114

Alfa AF: 0.739 Hom.: 5174

Bravo AF: 0.772

Asia WGS AF: 0.713 AC: 2476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.23
DANN	Benign	0.16
PhyloP100		-2.0
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: rs2395635; hg19: chr6-35671165;