rs9470079

Variant names:

• chr6-35675286-G-A
• rs9470079
• NM_004117.4:c.-20+13518C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-35675286-G-A
• chr6-35675286-G-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.-20+13518C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,218 control chromosomes in the GnomAD database, including 3,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars).

• Frequency: Genomes: 𝑓 0.19 (3023 hom., cov: 33)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: 0.903
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-20+13518C>T		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-32443C>T		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-20+13446C>T		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-20+13518C>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.-20+13518C>T		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-32443C>T		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-20+13446C>T		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-20+13518C>T		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29584 AN: 152100 Hom.: 3020 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.194 AC: 29593 AN: 152218 Hom.: 3023 Cov.: 33 AF XY: 0.199 AC XY: 14823 AN XY: 74434

African (AFR) AF: 0.238 AC: 9882 AN: 41520

American (AMR) AF: 0.168 AC: 2568 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1875 AN: 5192

South Asian (SAS) AF: 0.225 AC: 1089 AN: 4830

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11179 AN: 68008

Other (OTH) AF: 0.158 AC: 333 AN: 2112

Alfa AF: 0.176 Hom.: 294

Bravo AF: 0.194

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Susceptibility to severe depressive disorder Pathogenic:1

Jul 01, 2022

Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology

Significance: Likely risk allele

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.76
PhyloP100		0.90
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: rs9470079; hg19: chr6-35643063;