rs3777747

Variant names:

• chr6-35611225-A-G
• rs3777747
• NM_004117.4:c.508+7871T>C

Variant summary

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

The NM_004117.4(FKBP5):​c.508+7871T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,918 control chromosomes in the GnomAD database, including 15,265 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 0.45 (15265 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 22 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.508+7871T>C		intron_variant	Intron 5 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.508+7871T>C		intron_variant	Intron 6 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.508+7871T>C		intron_variant	Intron 5 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.508+7871T>C		intron_variant	Intron 5 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.508+7871T>C		intron_variant	Intron 5 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.508+7871T>C		intron_variant	Intron 6 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.508+7871T>C		intron_variant	Intron 5 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.508+7871T>C		intron_variant	Intron 5 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67584 AN: 151800 Hom.: 15257 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.445 AC: 67613 AN: 151918 Hom.: 15265 Cov.: 32 AF XY: 0.448 AC XY: 33278 AN XY: 74252

African (AFR) AF: 0.378 AC: 15638 AN: 41402

American (AMR) AF: 0.504 AC: 7691 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2007 AN: 3468

East Asian (EAS) AF: 0.610 AC: 3153 AN: 5166

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4822

European-Finnish (FIN) AF: 0.458 AC: 4822 AN: 10522

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30645 AN: 67968

Other (OTH) AF: 0.452 AC: 950 AN: 2104

Alfa AF: 0.460 Hom.: 25505

Bravo AF: 0.447

Asia WGS AF: 0.487 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.81
PhyloP100		0.31
Mutation Taster		=100/0	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: rs3777747; hg19: chr6-35579002;