20-1391053-A-G

Position:

• chr20-1391053-A-G

Variant summary

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

The NM_000801.5(FKBP1A):​c.85+1781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,080 control chromosomes in the GnomAD database, including 48,571 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 0.80 (48571 hom., cov: 30)
• Consequence: FKBP1A NM_000801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP1A	NM_000801.5	c.85+1781T>C		intron_variant		ENST00000400137.9	NP_000792.1
FKBP1A	NM_054014.4	c.85+1781T>C		intron_variant			NP_463460.1
FKBP1A	NM_001199786.2	c.85+1781T>C		intron_variant			NP_001186715.1
FKBP1A-SDCBP2	NR_037661.1	n.259+1781T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP1A	ENST00000400137.9	c.85+1781T>C		intron_variant		1	NM_000801.5	ENSP00000383003.4
ENSG00000274322	ENST00000617804.1	n.204+550T>C		intron_variant		4		ENSP00000479180.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120944 AN: 151962 Hom.: 48511 Cov.: 30

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.809

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

GnomAD4 genome AF: 0.796 AC: 121065 AN: 152080 Hom.: 48571 Cov.: 30 AF XY: 0.788 AC XY: 58600 AN XY: 74332

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.812

Alfa AF: 0.775 Hom.: 59682

Bravo AF: 0.818

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.7
DANN	Benign	0.51

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: rs1294690; hg19: chr20-1371697;