chr6-35595197-T-A

Variant names:

• chr6-35595197-T-A
• rs9366890
• NM_004117.4:c.665+2051A>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.665+2051A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,172 control chromosomes in the GnomAD database, including 51,834 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 0.82 (51834 hom., cov: 33)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.665+2051A>T		intron_variant	Intron 6 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.665+2051A>T		intron_variant	Intron 7 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.665+2051A>T		intron_variant	Intron 6 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.665+2051A>T		intron_variant	Intron 6 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.665+2051A>T		intron_variant	Intron 6 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.665+2051A>T		intron_variant	Intron 7 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.665+2051A>T		intron_variant	Intron 6 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.665+2051A>T		intron_variant	Intron 6 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125346 AN: 152054 Hom.: 51782 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.824 AC: 125455 AN: 152172 Hom.: 51834 Cov.: 33 AF XY: 0.825 AC XY: 61380 AN XY: 74402

African (AFR) AF: 0.839 AC: 34798 AN: 41466

American (AMR) AF: 0.834 AC: 12760 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2811 AN: 3472

East Asian (EAS) AF: 0.803 AC: 4164 AN: 5188

South Asian (SAS) AF: 0.726 AC: 3497 AN: 4820

European-Finnish (FIN) AF: 0.862 AC: 9130 AN: 10596

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55660 AN: 68012

Other (OTH) AF: 0.790 AC: 1671 AN: 2114

Alfa AF: 0.829 Hom.: 6502

Bravo AF: 0.824

Asia WGS AF: 0.763 AC: 2650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.036
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: rs9366890; hg19: chr6-35562974;