6-35617837-C-T

Variant names:

• chr6-35617837-C-T
• rs9368878
• NM_004117.4:c.508+1259G>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.508+1259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,012 control chromosomes in the GnomAD database, including 32,961 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 (32961 hom., cov: 31)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 7 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004117.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_004117.4	MANE Select	c.508+1259G>A		intron	N/A	NP_004108.1
	FKBP5	NM_001145775.3		c.508+1259G>A		intron	N/A	NP_001139247.1
	FKBP5	NM_001145776.2		c.508+1259G>A		intron	N/A	NP_001139248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.508+1259G>A		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.508+1259G>A		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.508+1259G>A		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99447 AN: 151894 Hom.: 32947 Cov.: 31

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.659

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: 0.655 AC: 99495 AN: 152012 Hom.: 32961 Cov.: 31 AF XY: 0.659 AC XY: 48995 AN XY: 74306

African (AFR) AF: 0.543 AC: 22468 AN: 41394

American (AMR) AF: 0.642 AC: 9812 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3575 AN: 5178

South Asian (SAS) AF: 0.649 AC: 3133 AN: 4830

European-Finnish (FIN) AF: 0.803 AC: 8491 AN: 10576

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.696 AC: 47306 AN: 67974

Other (OTH) AF: 0.633 AC: 1334 AN: 2108

Alfa AF: 0.671 Hom.: 5196

Bravo AF: 0.637

Asia WGS AF: 0.655 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.75
PhyloP100		0.032
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: rs9368878; hg19: chr6-35585614;