rs34866878

Variant names:

• chr6-35577165-G-A
• rs34866878
• NM_004117.4:c.1095C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004117.4(FKBP5):​c.1095C>T​(p.Asn365Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,613,930 control chromosomes in the GnomAD database, including 1,892 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 0.070 (753 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1139 hom.)
• Consequence: FKBP5 NM_004117.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 15 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]

ENSG00000228559 (HGNC:58100):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.1095C>T	p.Asn365Asn	synonymous_variant	Exon 10 of 11	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.1095C>T	p.Asn365Asn	synonymous_variant	Exon 11 of 12		NP_001139247.1
FKBP5	NM_001145776.2	c.1095C>T	p.Asn365Asn	synonymous_variant	Exon 10 of 11		NP_001139248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.1095C>T	p.Asn365Asn	synonymous_variant	Exon 10 of 11	1	NM_004117.4	ENSP00000349811.3

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10687 AN: 152024 Hom.: 748 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0674

GnomAD2 exomes AF: 0.0324 AC: 8138 AN: 251330 AF XY: 0.0281

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0248

Gnomad ASJ exome AF: 0.0577

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.0151

Gnomad NFE exome AF: 0.0249

Gnomad OTH exome AF: 0.0297

GnomAD4 exome AF: 0.0266 AC: 38884 AN: 1461786 Hom.: 1139 Cov.: 31 AF XY: 0.0254 AC XY: 18506 AN XY: 727196

African (AFR) AF: 0.199 AC: 6675 AN: 33468

American (AMR) AF: 0.0265 AC: 1185 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0549 AC: 1435 AN: 26124

East Asian (EAS) AF: 0.000756 AC: 30 AN: 39700

South Asian (SAS) AF: 0.00475 AC: 410 AN: 86256

European-Finnish (FIN) AF: 0.0138 AC: 735 AN: 53420

Middle Eastern (MID) AF: 0.0439 AC: 253 AN: 5768

European-Non Finnish (NFE) AF: 0.0235 AC: 26158 AN: 1111938

Other (OTH) AF: 0.0332 AC: 2003 AN: 60392

GnomAD4 genome AF: 0.0705 AC: 10721 AN: 152144 Hom.: 753 Cov.: 32 AF XY: 0.0691 AC XY: 5139 AN XY: 74386

African (AFR) AF: 0.189 AC: 7850 AN: 41446

American (AMR) AF: 0.0392 AC: 600 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4830

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0248 AC: 1684 AN: 68014

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0517 Hom.: 196

Bravo AF: 0.0776

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.0262

EpiControl AF: 0.0266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.65
DANN	Benign	0.58
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=98/2	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: rs34866878; hg19: chr6-35544942;