rs9470067

Variant names:

• chr6-35609079-G-A
• rs9470067
• NM_004117.4:c.508+10017C>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.508+10017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 152,214 control chromosomes in the GnomAD database, including 170 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 0.030 (170 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.508+10017C>T		intron_variant	Intron 5 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.508+10017C>T		intron_variant	Intron 6 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.508+10017C>T		intron_variant	Intron 5 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.508+10017C>T		intron_variant	Intron 5 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.508+10017C>T		intron_variant	Intron 5 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.508+10017C>T		intron_variant	Intron 6 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.508+10017C>T		intron_variant	Intron 5 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.508+10017C>T		intron_variant	Intron 5 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4637 AN: 152096 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00593

Gnomad OTH AF: 0.0383

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

GnomAD4 genome AF: 0.0305 AC: 4641 AN: 152214 Hom.: 170 Cov.: 32 AF XY: 0.0293 AC XY: 2178 AN XY: 74422

African (AFR) AF: 0.0858 AC: 3561 AN: 41522

American (AMR) AF: 0.0290 AC: 444 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00591 AC: 402 AN: 68004

Other (OTH) AF: 0.0374 AC: 79 AN: 2110

Alfa AF: 0.0142 Hom.: 15

Bravo AF: 0.0355

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.56
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism

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: rs9470067; hg19: chr6-35576856;