Variant 20-1370028-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000801.5(FKBP1A):c.*81A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,548,388 control chromosomes in the GnomAD database, including 148,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15307 hom., cov: 33)

Exomes 𝑓: 0.43 ( 133476 hom. )

Consequence

FKBP1A
NM_000801.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0490

Variant links:

Genes affected

FKBP1A (HGNC:3711): (FKBP prolyl isomerase 1A) 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. The protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels, and coordinates multi-protein complex formation of the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed. [provided by RefSeq, Sep 2008]

FKBP1A links:

SDCBP2-AS1 (HGNC:44314): (SDCBP2 antisense RNA 1)

SDCBP2-AS1 links:

FKBP1A-SDCBP2 (HGNC:):

FKBP1A-SDCBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 20-1370028-T-C is Benign according to our data. Variant chr20-1370028-T-C is described in ClinVar as [Benign]. Clinvar id is 1233437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
FKBP1A	NM_000801.5 linkuse as main transcript	c.*81A>G	3_prime_UTR_variant	5/5	ENST00000400137.9	NP_000792.1
FKBP1A-SDCBP2	NR_037661.1 linkuse as main transcript	n.259+22806A>G	intron_variant, non_coding_transcript_variant
SDCBP2-AS1	NR_040047.1 linkuse as main transcript	n.441-3050T>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP1A	ENST00000400137.9 linkuse as main transcript	c.*81A>G		3_prime_UTR_variant	5/5	1	NM_000801.5	ENSP00000383003	P1
SDCBP2-AS1	ENST00000609470.7 linkuse as main transcript	n.126-3050T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66832

AN:

152024

Hom.:

15311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.498

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.482

GnomAD3 exomes

AF:

0.386

AC:

56970

AN:

147768

Hom.:

12055

AF XY:

0.393

AC XY:

31232

AN XY:

79512

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.282

Gnomad ASJ exome

AF:

0.509

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.448

GnomAD4 exome

AF:

0.431

AC:

601241

AN:

1396246

Hom.:

133476

Cov.:

AF XY:

0.431

AC XY:

296836

AN XY:

688706

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.306

Gnomad4 ASJ exome

AF:

0.508

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.447

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.439

AC:

66848

AN:

152142

Hom.:

15307

Cov.:

AF XY:

0.428

AC XY:

31857

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.498

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.455

Gnomad4 OTH

AF:

0.479

Alfa

AF:

0.457

Hom.:

2975

Bravo

AF:

0.447

Asia WGS

AF:

0.255

AC:

891

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 22, 2019	This variant is associated with the following publications: (PMID: 30215102) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over