rs16878591

Variant names:

• chr6-35584850-A-G
• rs16878591
• NM_004117.4:c.840+2184T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004117.4(FKBP5):​c.840+2184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 985,368 control chromosomes in the GnomAD database, including 414 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 0.035 (127 hom., cov: 32)
  • Exomes 𝑓: 0.023 (287 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004117.4. 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
	FKBP5	NM_004117.4	MANE Select	c.840+2184T>C		intron	N/A	NP_004108.1
	FKBP5	NM_001145777.2		c.*2126T>C		3_prime_UTR	Exon 7 of 7	NP_001139249.1
	FKBP5	NM_001145775.3		c.840+2184T>C		intron	N/A	NP_001139247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.840+2184T>C		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.840+2184T>C		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.840+2184T>C		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5396 AN: 152160 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0234 AC: 19502 AN: 833090 Hom.: 287 Cov.: 31 AF XY: 0.0233 AC XY: 8969 AN XY: 384706

African (AFR) AF: 0.0826 AC: 1303 AN: 15782

American (AMR) AF: 0.0274 AC: 27 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 294 AN: 5152

East Asian (EAS) AF: 0.00138 AC: 5 AN: 3630

South Asian (SAS) AF: 0.00383 AC: 63 AN: 16460

European-Finnish (FIN) AF: 0.00725 AC: 2 AN: 276

Middle Eastern (MID) AF: 0.0383 AC: 62 AN: 1620

European-Non Finnish (NFE) AF: 0.0224 AC: 17040 AN: 761888

Other (OTH) AF: 0.0259 AC: 706 AN: 27298

GnomAD4 genome AF: 0.0355 AC: 5399 AN: 152278 Hom.: 127 Cov.: 32 AF XY: 0.0342 AC XY: 2550 AN XY: 74474

African (AFR) AF: 0.0694 AC: 2884 AN: 41538

American (AMR) AF: 0.0256 AC: 391 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10606

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0239 AC: 1628 AN: 68024

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0280 Hom.: 93

Bravo AF: 0.0377

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		2.1
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: rs16878591; hg19: chr6-35552627;