rs1043805

Variant names:

• chr6-35573655-T-A
• rs1043805
• NM_004117.4:c.*2180A>T

Variant summary

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

The NM_004117.4(FKBP5):​c.*2180A>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 0.823 in 151,980 control chromosomes in the GnomAD database, including 51,523 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 0.82 (51523 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FKBP5 NM_004117.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 14 publications found

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]

ENSG00000228559 (HGNC:58100):

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 (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.*2180A>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.*2180A>T		3_prime_UTR_variant	Exon 12 of 12		NP_001139247.1
FKBP5	NM_001145776.2	c.*2180A>T		3_prime_UTR_variant	Exon 11 of 11		NP_001139248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.*2180A>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_004117.4	ENSP00000349811.3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 124909 AN: 151862 Hom.: 51474 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.790

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.823 AC: 125014 AN: 151980 Hom.: 51523 Cov.: 32 AF XY: 0.823 AC XY: 61150 AN XY: 74318

African (AFR) AF: 0.812 AC: 33613 AN: 41410

American (AMR) AF: 0.829 AC: 12657 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2669 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4092 AN: 5180

South Asian (SAS) AF: 0.717 AC: 3458 AN: 4822

European-Finnish (FIN) AF: 0.867 AC: 9164 AN: 10572

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.834 AC: 56654 AN: 67952

Other (OTH) AF: 0.784 AC: 1655 AN: 2110

Alfa AF: 0.834 Hom.: 6438

Bravo AF: 0.821

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.41
DANN	Benign	0.23
PhyloP100		1.2
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: rs1043805; hg19: chr6-35541432; COSMIC: COSV61881858;