rs3800373

Positions:

• chr6-35574699-C-A
• chr6-35574699-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004117.4(FKBP5):​c.*1136G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,464 control chromosomes in the GnomAD database, including 35,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35446 hom., cov: 33)
  • Exomes 𝑓: 0.81 (139 hom.)
• Consequence: FKBP5 NM_004117.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.222

Genes affected

FKBP5 (HGNC:3721): (FKBP prolyl isomerase 5) 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. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

LOC101929309 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-35574699-C-A is Benign according to our data. Variant chr6-35574699-C-A is described in ClinVar as [Benign]. Clinvar id is 1279819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_004117.4	c.*1136G>T		3_prime_UTR_variant	11/11	ENST00000357266.9
LOC101929309	XR_242006.4	n.182-18331C>A		intron_variant, non_coding_transcript_variant
FKBP5	NM_001145775.3	c.*1136G>T		3_prime_UTR_variant	12/12
FKBP5	NM_001145776.2	c.*1136G>T		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000357266.9	c.*1136G>T		3_prime_UTR_variant	11/11	1	NM_004117.4	P1
FKBP5	ENST00000536438.5	c.*1136G>T		3_prime_UTR_variant	12/12	1		P1
FKBP5	ENST00000539068.5	c.*1136G>T		3_prime_UTR_variant	11/11	1		P1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103224 AN: 151932 Hom.: 35419 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.661

GnomAD4 exome AF: 0.813 AC: 335 AN: 412 Hom.: 139 Cov.: 0 AF XY: 0.836 AC XY: 209 AN XY: 250

Gnomad4 FIN exome AF: 0.814

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.679 AC: 103294 AN: 152052 Hom.: 35446 Cov.: 33 AF XY: 0.684 AC XY: 50846 AN XY: 74330

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.656

Alfa AF: 0.711 Hom.: 66774

Bravo AF: 0.665

Asia WGS AF: 0.688 AC: 2389 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 18, 2019

This variant is associated with the following publications: (PMID: 30150364, 31071710) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.50

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: rs3800373; hg19: chr6-35542476; COSMIC: COSV61881577;