rs9394309

Variant names:

• chr6-35654004-G-A
• rs9394309
• NM_004117.4:c.-19-11161C>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.-19-11161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,090 control chromosomes in the GnomAD database, including 41,946 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 0.74 (41946 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 37 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-19-11161C>T		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-11161C>T		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-19-11161C>T		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-19-11161C>T		intron_variant	Intron 1 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-19-11161C>T		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-11161C>T		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-19-11161C>T		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-19-11161C>T		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112510 AN: 151970 Hom.: 41891 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.740 AC: 112622 AN: 152090 Hom.: 41946 Cov.: 32 AF XY: 0.744 AC XY: 55311 AN XY: 74332

African (AFR) AF: 0.814 AC: 33796 AN: 41514

American (AMR) AF: 0.715 AC: 10928 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2748 AN: 3472

East Asian (EAS) AF: 0.774 AC: 4013 AN: 5184

South Asian (SAS) AF: 0.678 AC: 3267 AN: 4822

European-Finnish (FIN) AF: 0.780 AC: 8218 AN: 10542

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47223 AN: 67966

Other (OTH) AF: 0.730 AC: 1537 AN: 2106

Alfa AF: 0.706 Hom.: 22303

Bravo AF: 0.740

Asia WGS AF: 0.725 AC: 2516 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.21
PhyloP100		-0.54
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: rs9394309; hg19: chr6-35621781;