rs10947564

chr6-35688197-T-C

Variant summary

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

The NM_004117.4(FKBP5):c.-20+607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,176 control chromosomes in the GnomAD database, including 2,405 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 0.17 (2405 hom., cov: 33)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP5	NM_004117.4	c.-20+607A>G		intron_variant		ENST00000357266.9
FKBP5	NM_001145775.3	c.-20+32131A>G		intron_variant
FKBP5	NM_001145776.2	c.-20+535A>G		intron_variant
FKBP5	NM_001145777.2	c.-20+607A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP5	ENST00000357266.9	c.-20+607A>G		intron_variant		1	NM_004117.4	P1
FKBP5	ENST00000536438.5	c.-20+32131A>G		intron_variant		1		P1
FKBP5	ENST00000539068.5	c.-20+535A>G		intron_variant		1		P1
FKBP5	ENST00000542713.1	c.-20+607A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26463 AN: 152060 Hom.: 2404 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.174 AC: 26471 AN: 152176 Hom.: 2405 Cov.: 33 AF XY: 0.179 AC XY: 13347 AN XY: 74406

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.144

Alfa AF: 0.170 Hom.: 477

Bravo AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	10
Dann	Benign	0.60

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: rs10947564; hg19: chr6-35655974;