20-1375617-G-C

Variant names:

• chr20-1375617-G-C
• rs6074549
• NM_000801.5:c.86-14C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000801.5(FKBP1A):​c.86-14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,575,084 control chromosomes in the GnomAD database, including 784,895 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 0.99 (74790 hom., cov: 29)
  • Exomes 𝑓: 1.0 (710105 hom.)
• Consequence: FKBP1A NM_000801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 8 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]

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

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1A	NM_000801.5	MANE Select	c.86-14C>G		intron	N/A	NP_000792.1
	FKBP1A	NM_054014.4		c.86-14C>G		intron	N/A	NP_463460.1
	FKBP1A	NM_001199786.2		c.86-3377C>G		intron	N/A	NP_001186715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1A	ENST00000400137.9	TSL:1 MANE Select	c.86-14C>G		intron	N/A	ENSP00000383003.4
	FKBP1A	ENST00000381719.8	TSL:1	c.86-14C>G		intron	N/A	ENSP00000371138.3
	FKBP1A	ENST00000618612.5	TSL:1	c.86-3377C>G		intron	N/A	ENSP00000478093.1

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150752 AN: 152068 Hom.: 74736 Cov.: 29

Gnomad AFR AF: 0.970

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.994

GnomAD2 exomes AF: 0.998 AC: 250368 AN: 250914 AF XY: 0.998

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.999 AC: 1421541 AN: 1422898 Hom.: 710105 Cov.: 24 AF XY: 0.999 AC XY: 710273 AN XY: 710858

African (AFR) AF: 0.969 AC: 31752 AN: 32776

American (AMR) AF: 0.998 AC: 44588 AN: 44672

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25858 AN: 25858

East Asian (EAS) AF: 1.00 AC: 39489 AN: 39490

South Asian (SAS) AF: 1.00 AC: 85374 AN: 85384

European-Finnish (FIN) AF: 1.00 AC: 53402 AN: 53402

Middle Eastern (MID) AF: 0.998 AC: 5691 AN: 5700

European-Non Finnish (NFE) AF: 1.00 AC: 1076450 AN: 1076540

Other (OTH) AF: 0.998 AC: 58937 AN: 59076

GnomAD4 genome AF: 0.991 AC: 150865 AN: 152186 Hom.: 74790 Cov.: 29 AF XY: 0.992 AC XY: 73776 AN XY: 74400

African (AFR) AF: 0.970 AC: 40238 AN: 41480

American (AMR) AF: 0.996 AC: 15237 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 1.00 AC: 4817 AN: 4818

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68009 AN: 68020

Other (OTH) AF: 0.994 AC: 2098 AN: 2110

Alfa AF: 0.996 Hom.: 13878

Bravo AF: 0.990

Asia WGS AF: 0.997 AC: 3469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	18
DANN	Benign	0.55
PhyloP100		1.6
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6074549; hg19: chr20-1356261;