rs3798347

Variant names:

• chr6-35633999-A-T
• rs3798347
• NM_004117.4:c.250+3015T>A

Variant summary

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

The NM_004117.4(FKBP5):​c.250+3015T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,732 control chromosomes in the GnomAD database, including 32,830 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 0.65 (32830 hom., cov: 29)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.250+3015T>A		intron_variant	Intron 3 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.250+3015T>A		intron_variant	Intron 4 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.250+3015T>A		intron_variant	Intron 3 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.250+3015T>A		intron_variant	Intron 3 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.250+3015T>A		intron_variant	Intron 3 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.250+3015T>A		intron_variant	Intron 4 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.250+3015T>A		intron_variant	Intron 3 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.250+3015T>A		intron_variant	Intron 3 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99140 AN: 151614 Hom.: 32816 Cov.: 29

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.654 AC: 99188 AN: 151732 Hom.: 32830 Cov.: 29 AF XY: 0.659 AC XY: 48837 AN XY: 74138

African (AFR) AF: 0.540 AC: 22323 AN: 41336

American (AMR) AF: 0.642 AC: 9775 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2523 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3529 AN: 5136

South Asian (SAS) AF: 0.652 AC: 3132 AN: 4804

European-Finnish (FIN) AF: 0.802 AC: 8436 AN: 10514

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47275 AN: 67936

Other (OTH) AF: 0.633 AC: 1335 AN: 2108

Alfa AF: 0.678 Hom.: 4340

Bravo AF: 0.636

Asia WGS AF: 0.655 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.47
PhyloP100		-0.94
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: rs3798347; hg19: chr6-35601776;