rs10498734

Positions:

• chr6-35591996-A-C

Variant summary

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

The NM_004117.4(FKBP5):​c.666-776T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 152,290 control chromosomes in the GnomAD database, including 462 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 0.064 (462 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.666-776T>G		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.666-776T>G		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.666-776T>G		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.666-4879T>G		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.666-776T>G		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.666-776T>G		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.666-776T>G		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.666-4879T>G		intron_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9702 AN: 152172 Hom.: 461 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0637 AC: 9701 AN: 152290 Hom.: 462 Cov.: 32 AF XY: 0.0607 AC XY: 4524 AN XY: 74480

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00617

Gnomad4 SAS AF: 0.0538

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0772 Hom.: 100

Bravo AF: 0.0685

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.58

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: rs10498734; hg19: chr6-35559773;