20-1388554-C-T

Variant names:

• chr20-1388554-C-T
• rs1294689
• NM_000801.5:c.85+4280G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000801.5(FKBP1A):​c.85+4280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,148 control chromosomes in the GnomAD database, including 41,176 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 0.73 (41176 hom., cov: 32)
• Consequence: FKBP1A NM_000801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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]

ENSG00000274322 (HGNC:):

FKBP1A-SDCBP2 (HGNC:41997): (FKBP1A-SDCBP2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring FK506 binding protein 1A, 12kDa and syndecan binding protein (syntenin) 2 genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -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 = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP1A	NM_000801.5	c.85+4280G>A		intron_variant	Intron 2 of 4	ENST00000400137.9	NP_000792.1
FKBP1A	NM_054014.4	c.85+4280G>A		intron_variant	Intron 2 of 3		NP_463460.1
FKBP1A	NM_001199786.2	c.85+4280G>A		intron_variant	Intron 2 of 3		NP_001186715.1
FKBP1A-SDCBP2	NR_037661.1	n.259+4280G>A		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP1A	ENST00000400137.9	c.85+4280G>A		intron_variant	Intron 2 of 4	1	NM_000801.5	ENSP00000383003.4
ENSG00000274322	ENST00000617804.1	n.204+3049G>A		intron_variant	Intron 3 of 5	4		ENSP00000479180.1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111298 AN: 152030 Hom.: 41114 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.732 AC: 111424 AN: 152148 Hom.: 41176 Cov.: 32 AF XY: 0.727 AC XY: 54068 AN XY: 74384

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.740

Alfa AF: 0.708 Hom.: 36180

Bravo AF: 0.751

Asia WGS AF: 0.716 AC: 2491 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	3.9
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs1294689; hg19: chr20-1369198;