rs10947563

Positions:

• chr6-35685660-G-A
• chr6-35685660-G-T

Variant summary

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

The NM_004117.4(FKBP5):​c.-20+3144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,064 control chromosomes in the GnomAD database, including 45,194 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 0.77 (45194 hom., cov: 31)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-20+3144C>T		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-20+34668C>T		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.-20+3072C>T		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.-20+3144C>T		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-20+3144C>T		intron_variant		1	NM_004117.4	ENSP00000349811	P1
FKBP5	ENST00000536438.5	c.-20+34668C>T		intron_variant		1		ENSP00000444810	P1
FKBP5	ENST00000539068.5	c.-20+3072C>T		intron_variant		1		ENSP00000441205	P1
FKBP5	ENST00000542713.1	c.-20+3144C>T		intron_variant		2		ENSP00000442340

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116598 AN: 151946 Hom.: 45136 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.768 AC: 116715 AN: 152064 Hom.: 45194 Cov.: 31 AF XY: 0.769 AC XY: 57175 AN XY: 74324

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.752

Alfa AF: 0.720 Hom.: 9121

Bravo AF: 0.770

Asia WGS AF: 0.732 AC: 2541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.59

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: rs10947563; hg19: chr6-35653437;