NM_004117.4:c.251-4693A>G

Variant names:

• chr6-35624967-T-C
• rs7748266
• NM_004117.4:c.251-4693A>G

Variant summary

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

The NM_004117.4(FKBP5):​c.251-4693A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,230 control chromosomes in the GnomAD database, including 54,683 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 0.85 (54683 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 32 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.251-4693A>G		intron_variant	Intron 3 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.251-4693A>G		intron_variant	Intron 4 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.251-4693A>G		intron_variant	Intron 3 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.251-4693A>G		intron_variant	Intron 3 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.251-4693A>G		intron_variant	Intron 3 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.251-4693A>G		intron_variant	Intron 4 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.251-4693A>G		intron_variant	Intron 3 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.251-4693A>G		intron_variant	Intron 3 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128729 AN: 152112 Hom.: 54630 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.846 AC: 128840 AN: 152230 Hom.: 54683 Cov.: 32 AF XY: 0.845 AC XY: 62882 AN XY: 74424

African (AFR) AF: 0.896 AC: 37232 AN: 41542

American (AMR) AF: 0.844 AC: 12891 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2816 AN: 3472

East Asian (EAS) AF: 0.784 AC: 4056 AN: 5174

South Asian (SAS) AF: 0.721 AC: 3483 AN: 4828

European-Finnish (FIN) AF: 0.862 AC: 9131 AN: 10598

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56573 AN: 68026

Other (OTH) AF: 0.805 AC: 1697 AN: 2108

Alfa AF: 0.831 Hom.: 31141

Bravo AF: 0.849

Asia WGS AF: 0.760 AC: 2642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.60
PhyloP100		-0.32
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: rs7748266; hg19: chr6-35592744;