Variant 12-2799979-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000001008.6(FKBP4):c.762+39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 1,612,842 control chromosomes in the GnomAD database, including 3,273 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 0.065 ( 447 hom., cov: 33)

Exomes 𝑓: 0.050 ( 2826 hom. )

Consequence

FKBP4
ENST00000001008.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

FKBP4 (HGNC:3720): (FKBP prolyl isomerase 4) 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 has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone receptors. This protein correlates strongly with adeno-associated virus type 2 vectors (AAV) resulting in a significant increase in AAV-mediated transgene expression in human cell lines. Thus this encoded protein is thought to have important implications for the optimal use of AAV vectors in human gene therapy. The human genome contains several non-transcribed pseudogenes similar to this gene. [provided by RefSeq, Sep 2008]

FKBP4 links:

(HGNC:):

links:

ITFG2-AS1 (HGNC:53128): (ITFG2 antisense RNA 1)

ITFG2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
FKBP4	NM_002014.4 linkuse as main transcript	c.762+39C>G	intron_variant	ENST00000001008.6	NP_002005.1
ITFG2-AS1	NR_146317.1 linkuse as main transcript	n.364-3033G>C	intron_variant, non_coding_transcript_variant
FKBP4	XM_047428539.1 linkuse as main transcript	c.627+39C>G	intron_variant		XP_047284495.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
FKBP4	ENST00000001008.6 linkuse as main transcript	c.762+39C>G	intron_variant	1	NM_002014.4	ENSP00000001008	P1
	ENST00000547042.1 linkuse as main transcript	n.151-2707G>C	intron_variant, non_coding_transcript_variant	3
ITFG2-AS1	ENST00000547834.1 linkuse as main transcript	n.342-3033G>C	intron_variant, non_coding_transcript_variant	5
FKBP4	ENST00000543037.1 linkuse as main transcript	n.569+39C>G	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0650

AC:

9883

AN:

152126

Hom.:

448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0748

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.0686

Gnomad FIN

AF:

0.0361

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0435

Gnomad OTH

AF:

0.0755

GnomAD3 exomes

AF:

0.0687

AC:

17273

AN:

251398

Hom.:

925

AF XY:

0.0652

AC XY:

8864

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.0389

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.0620

Gnomad FIN exome

AF:

0.0345

Gnomad NFE exome

AF:

0.0418

Gnomad OTH exome

AF:

0.0564

GnomAD4 exome

AF:

0.0504

AC:

73655

AN:

1460598

Hom.:

2826

Cov.:

AF XY:

0.0503

AC XY:

36523

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.0738

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.0395

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.0614

Gnomad4 FIN exome

AF:

0.0360

Gnomad4 NFE exome

AF:

0.0404

Gnomad4 OTH exome

AF:

0.0625

GnomAD4 genome

AF:

0.0651

AC:

9905

AN:

152244

Hom.:

447

Cov.:

AF XY:

0.0663

AC XY:

4935

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0750

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0429

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.0682

Gnomad4 FIN

AF:

0.0361

Gnomad4 NFE

AF:

0.0435

Gnomad4 OTH

AF:

0.0771

Alfa

AF:

0.0517

Hom.:

Bravo

AF:

0.0707

Asia WGS

AF:

0.153

AC:

530

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.5

DANN

Benign

0.47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over