6-35612521-T-C

Variant names:

• chr6-35612521-T-C
• rs6457836
• NM_004117.4:c.508+6575A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004117.4(FKBP5):​c.508+6575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,254 control chromosomes in the GnomAD database, including 53,899 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 0.84 (53899 hom., cov: 33)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.508+6575A>G		intron_variant	Intron 5 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.508+6575A>G		intron_variant	Intron 6 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.508+6575A>G		intron_variant	Intron 5 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.508+6575A>G		intron_variant	Intron 5 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.508+6575A>G		intron_variant	Intron 5 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.508+6575A>G		intron_variant	Intron 6 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.508+6575A>G		intron_variant	Intron 5 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.508+6575A>G		intron_variant	Intron 5 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127846 AN: 152136 Hom.: 53845 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.840 AC: 127958 AN: 152254 Hom.: 53899 Cov.: 33 AF XY: 0.839 AC XY: 62471 AN XY: 74436

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.800

Alfa AF: 0.844 Hom.: 7139

Bravo AF: 0.842

Asia WGS AF: 0.761 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs6457836; hg19: chr6-35580298;