NM_004117.4:c.-19-4124T>C

Variant names:

• chr6-35646967-A-G
• rs17542466
• NM_004117.4:c.-19-4124T>C

Variant summary

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

The NM_004117.4(FKBP5):​c.-19-4124T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,248 control chromosomes in the GnomAD database, including 2,628 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 0.16 (2628 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-19-4124T>C		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-4124T>C		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-19-4124T>C		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-19-4124T>C		intron_variant	Intron 1 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-19-4124T>C		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-4124T>C		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-19-4124T>C		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-19-4124T>C		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24573 AN: 152128 Hom.: 2626 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24580 AN: 152248 Hom.: 2628 Cov.: 32 AF XY: 0.164 AC XY: 12216 AN XY: 74426

African (AFR) AF: 0.0400 AC: 1664 AN: 41572

American (AMR) AF: 0.102 AC: 1553 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3472

East Asian (EAS) AF: 0.0557 AC: 289 AN: 5190

South Asian (SAS) AF: 0.177 AC: 854 AN: 4824

European-Finnish (FIN) AF: 0.330 AC: 3496 AN: 10584

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15590 AN: 67998

Other (OTH) AF: 0.130 AC: 274 AN: 2114

Alfa AF: 0.113 Hom.: 217

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.71
PhyloP100		0.58
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: rs17542466; hg19: chr6-35614744;