NM_000801.5:c.85+4280G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000801.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1A	NM_000801.5	MANE Select	c.85+4280G>A		intron	N/A	NP_000792.1	P62942
	FKBP1A	NM_054014.4		c.85+4280G>A		intron	N/A	NP_463460.1	P62942
	FKBP1A	NM_001199786.2		c.85+4280G>A		intron	N/A	NP_001186715.1	A0A087WTS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1A	ENST00000400137.9	TSL:1 MANE Select	c.85+4280G>A		intron	N/A	ENSP00000383003.4	P62942
	FKBP1A	ENST00000381719.8	TSL:1	c.85+4280G>A		intron	N/A	ENSP00000371138.3	P62942
	FKBP1A	ENST00000618612.5	TSL:1	c.85+4280G>A		intron	N/A	ENSP00000478093.1	A0A087WTS4

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

African (AFR) AF: 0.833 AC: 34579 AN: 41522

American (AMR) AF: 0.721 AC: 11031 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2515 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4061 AN: 5162

South Asian (SAS) AF: 0.688 AC: 3317 AN: 4820

European-Finnish (FIN) AF: 0.590 AC: 6243 AN: 10584

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47268 AN: 67972

Other (OTH) AF: 0.740 AC: 1562 AN: 2110

Alfa AF: 0.709 Hom.: 44316

Bravo AF: 0.751

Asia WGS AF: 0.716 AC: 2491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.62
PhyloP100		-0.13
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: rs1294689; hg19: chr20-1369198;