6-35651777-G-A

Variant names:

• chr6-35651777-G-A
• rs1475774
• NM_004117.4:c.-19-8934C>T

Variant summary

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

The NM_004117.4(FKBP5):​c.-19-8934C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 218,480 control chromosomes in the GnomAD database, including 200 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 0.043 (175 hom., cov: 32)
  • Exomes 𝑓: 0.023 (25 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• 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]

ENSG00000287458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 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.-19-8934C>T		intron	N/A	NP_004108.1
	FKBP5	NM_001145775.3		c.-19-8934C>T		intron	N/A	NP_001139247.1
	FKBP5	NM_001145776.2		c.-19-8934C>T		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.-19-8934C>T		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.-19-8934C>T		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.-19-8934C>T		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6478 AN: 152038 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0563

Gnomad EAS AF: 0.0555

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.0229 AC: 1516 AN: 66324 Hom.: 25 Cov.: 4 AF XY: 0.0220 AC XY: 767 AN XY: 34802

African (AFR) AF: 0.0843 AC: 97 AN: 1150

American (AMR) AF: 0.0516 AC: 59 AN: 1144

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 59 AN: 1030

East Asian (EAS) AF: 0.0603 AC: 49 AN: 812

South Asian (SAS) AF: 0.00636 AC: 45 AN: 7070

European-Finnish (FIN) AF: 0.0154 AC: 29 AN: 1882

Middle Eastern (MID) AF: 0.0425 AC: 9 AN: 212

European-Non Finnish (NFE) AF: 0.0217 AC: 1096 AN: 50548

Other (OTH) AF: 0.0295 AC: 73 AN: 2476

GnomAD4 genome AF: 0.0426 AC: 6484 AN: 152156 Hom.: 175 Cov.: 32 AF XY: 0.0423 AC XY: 3150 AN XY: 74400

African (AFR) AF: 0.0793 AC: 3291 AN: 41488

American (AMR) AF: 0.0487 AC: 745 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0563 AC: 195 AN: 3464

East Asian (EAS) AF: 0.0557 AC: 289 AN: 5192

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4822

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10586

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1636 AN: 68002

Other (OTH) AF: 0.0422 AC: 89 AN: 2110

Alfa AF: 0.0301 Hom.: 144

Bravo AF: 0.0466

Asia WGS AF: 0.0300 AC: 105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.20
PhyloP100		-0.51
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: rs1475774; hg19: chr6-35619554;