rs3798346

Variant names:

• chr6-35594863-A-G
• rs3798346
• NM_004117.4:c.665+2385T>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.665+2385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,240 control chromosomes in the GnomAD database, including 2,760 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 0.17 (2760 hom., cov: 33)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.665+2385T>C		intron_variant	Intron 6 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.665+2385T>C		intron_variant	Intron 7 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.665+2385T>C		intron_variant	Intron 6 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.665+2385T>C		intron_variant	Intron 6 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.665+2385T>C		intron_variant	Intron 6 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.665+2385T>C		intron_variant	Intron 7 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.665+2385T>C		intron_variant	Intron 6 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.665+2385T>C		intron_variant	Intron 6 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25188 AN: 152120 Hom.: 2758 Cov.: 33

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.165 AC: 25195 AN: 152240 Hom.: 2760 Cov.: 33 AF XY: 0.168 AC XY: 12468 AN XY: 74410

African (AFR) AF: 0.0414 AC: 1722 AN: 41558

American (AMR) AF: 0.107 AC: 1638 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3470

East Asian (EAS) AF: 0.0519 AC: 269 AN: 5184

South Asian (SAS) AF: 0.179 AC: 865 AN: 4828

European-Finnish (FIN) AF: 0.327 AC: 3464 AN: 10584

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16076 AN: 68008

Other (OTH) AF: 0.134 AC: 283 AN: 2114

Alfa AF: 0.196 Hom.: 3606

Bravo AF: 0.142

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.67
PhyloP100		0.28
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: rs3798346; hg19: chr6-35562640;