rs17614642

Variant names:

• chr6-35654144-T-C
• rs17614642
• NM_004117.4:c.-19-11301A>G

Variant summary

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

The NM_004117.4(FKBP5):​c.-19-11301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 152,282 control chromosomes in the GnomAD database, including 361 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 0.058 (361 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0853 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.-19-11301A>G		intron	N/A	NP_004108.1
	FKBP5	NM_001145775.3		c.-19-11301A>G		intron	N/A	NP_001139247.1
	FKBP5	NM_001145776.2		c.-19-11301A>G		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.-19-11301A>G		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.-19-11301A>G		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.-19-11301A>G		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8767 AN: 152164 Hom.: 360 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0576 AC: 8769 AN: 152282 Hom.: 361 Cov.: 32 AF XY: 0.0577 AC XY: 4293 AN XY: 74460

African (AFR) AF: 0.0151 AC: 626 AN: 41572

American (AMR) AF: 0.0353 AC: 540 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4828

European-Finnish (FIN) AF: 0.134 AC: 1423 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0872 AC: 5928 AN: 68006

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0569 Hom.: 129

Bravo AF: 0.0493

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.5
DANN	Benign	0.76
PhyloP100		0.33
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: rs17614642; hg19: chr6-35621921;