rs3800373

Variant names:

• chr6-35574699-C-A
• rs3800373
• NM_004117.4:c.*1136G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 227 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 -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 VariationId 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 rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.*1136G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.*1136G>T		3_prime_UTR_variant	Exon 12 of 12		NP_001139247.1
FKBP5	NM_001145776.2	c.*1136G>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.*1136G>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_004117.4	ENSP00000349811.3

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

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) AF: 0.814 AC: 332 AN: 408

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AF: 0.750 AC: 3 AN: 4

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

African (AFR) AF: 0.572 AC: 23706 AN: 41420

American (AMR) AF: 0.675 AC: 10316 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2475 AN: 3468

East Asian (EAS) AF: 0.742 AC: 3831 AN: 5162

South Asian (SAS) AF: 0.664 AC: 3203 AN: 4822

European-Finnish (FIN) AF: 0.813 AC: 8615 AN: 10592

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.718 AC: 48805 AN: 67988

Other (OTH) AF: 0.656 AC: 1385 AN: 2110

Alfa AF: 0.704 Hom.: 152659

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

Jan 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.22
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: rs3800373; hg19: chr6-35542476; COSMIC: COSV61881577;