NM_004117.4:c.841-238C>T

Variant names:

• chr6-35580459-G-A
• rs7757037
• NM_004117.4:c.841-238C>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.841-238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 373,696 control chromosomes in the GnomAD database, including 43,104 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 0.45 (15525 hom., cov: 28)
  • Exomes 𝑓: 0.50 (27579 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 30 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 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.841-238C>T		intron	N/A	NP_004108.1
	FKBP5	NM_001145775.3		c.841-238C>T		intron	N/A	NP_001139247.1
	FKBP5	NM_001145776.2		c.841-238C>T		intron	N/A	NP_001139248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.841-238C>T		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.841-238C>T		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.841-238C>T		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 67782 AN: 149706 Hom.: 15519 Cov.: 28

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.496 AC: 110938 AN: 223888 Hom.: 27579 AF XY: 0.495 AC XY: 56735 AN XY: 114620

African (AFR) AF: 0.388 AC: 2655 AN: 6834

American (AMR) AF: 0.531 AC: 4275 AN: 8056

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 4507 AN: 8158

East Asian (EAS) AF: 0.630 AC: 12276 AN: 19498

South Asian (SAS) AF: 0.466 AC: 3304 AN: 7086

European-Finnish (FIN) AF: 0.478 AC: 7806 AN: 16338

Middle Eastern (MID) AF: 0.546 AC: 620 AN: 1136

European-Non Finnish (NFE) AF: 0.482 AC: 68422 AN: 142100

Other (OTH) AF: 0.482 AC: 7073 AN: 14682

GnomAD4 genome AF: 0.453 AC: 67805 AN: 149808 Hom.: 15525 Cov.: 28 AF XY: 0.455 AC XY: 33214 AN XY: 72958

African (AFR) AF: 0.372 AC: 15137 AN: 40672

American (AMR) AF: 0.506 AC: 7611 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1802 AN: 3452

East Asian (EAS) AF: 0.617 AC: 3125 AN: 5066

South Asian (SAS) AF: 0.450 AC: 2134 AN: 4742

European-Finnish (FIN) AF: 0.480 AC: 4777 AN: 9954

Middle Eastern (MID) AF: 0.517 AC: 150 AN: 290

European-Non Finnish (NFE) AF: 0.468 AC: 31604 AN: 67602

Other (OTH) AF: 0.456 AC: 956 AN: 2098

Alfa AF: 0.466 Hom.: 56317

Bravo AF: 0.451

Asia WGS AF: 0.496 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.61
PhyloP100		-0.96
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: rs7757037; hg19: chr6-35548236;