NM_004117.4:c.-20+1336C>T

Variant names:

• chr6-35687468-G-A
• rs3800372
• NM_004117.4:c.-20+1336C>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+1336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,070 control chromosomes in the GnomAD database, including 31,171 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 0.64 (31171 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-20+1336C>T		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-20+32860C>T		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-20+1264C>T		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-20+1336C>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+1336C>T		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-20+32860C>T		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-20+1264C>T		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-20+1336C>T		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96818 AN: 151948 Hom.: 31155 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.637 AC: 96872 AN: 152070 Hom.: 31171 Cov.: 32 AF XY: 0.642 AC XY: 47742 AN XY: 74326

African (AFR) AF: 0.534 AC: 22121 AN: 41446

American (AMR) AF: 0.640 AC: 9781 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2525 AN: 3472

East Asian (EAS) AF: 0.678 AC: 3510 AN: 5180

South Asian (SAS) AF: 0.662 AC: 3190 AN: 4816

European-Finnish (FIN) AF: 0.764 AC: 8080 AN: 10570

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45495 AN: 67992

Other (OTH) AF: 0.638 AC: 1346 AN: 2110

Alfa AF: 0.626 Hom.: 4617

Bravo AF: 0.624

Asia WGS AF: 0.654 AC: 2271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.69
PhyloP100		0.36
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: rs3800372; hg19: chr6-35655245;