ENST00000539068.5:c.-74A>G

Variant names:

• chr6-35688786-T-C
• rs9462103
• ENST00000539068.5:c.-74A>G

Variant summary

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

The ENST00000539068.5(FKBP5):​c.-74A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 150,640 control chromosomes in the GnomAD database, including 45,766 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 0.78 (45753 hom., cov: 33)
  • Exomes 𝑓: 0.63 (13 hom.)
• Consequence: FKBP5 ENST00000539068.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-20+18A>G		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145776.2	c.-74A>G		5_prime_UTR_variant	Exon 1 of 11		NP_001139248.1
FKBP5	NM_001145775.3	c.-20+31542A>G		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145777.2	c.-20+18A>G		intron_variant	Intron 1 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000539068.5	c.-74A>G		5_prime_UTR_variant	Exon 1 of 11	1		ENSP00000441205.1
FKBP5	ENST00000357266.9	c.-20+18A>G		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-20+31542A>G		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000542713.1	c.-20+18A>G		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 116599 AN: 150470 Hom.: 45696 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.629 AC: 39 AN: 62 Hom.: 13 Cov.: 0 AF XY: 0.583 AC XY: 28 AN XY: 48

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.607 AC: 34 AN: 56

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.775 AC: 116710 AN: 150578 Hom.: 45753 Cov.: 33 AF XY: 0.776 AC XY: 57097 AN XY: 73560

African (AFR) AF: 0.903 AC: 37341 AN: 41362

American (AMR) AF: 0.735 AC: 11147 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2732 AN: 3450

East Asian (EAS) AF: 0.776 AC: 3975 AN: 5124

South Asian (SAS) AF: 0.678 AC: 3275 AN: 4828

European-Finnish (FIN) AF: 0.781 AC: 7833 AN: 10026

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.712 AC: 47931 AN: 67338

Other (OTH) AF: 0.757 AC: 1583 AN: 2090

Alfa AF: 0.745 Hom.: 5161

Bravo AF: 0.780

Asia WGS AF: 0.720 AC: 2267 AN: 3156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		-0.57
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9462103; hg19: chr6-35656563;