6-35642904-T-C

Position:

• chr6-35642904-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.-19-61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 1,195,682 control chromosomes in the GnomAD database, including 437,250 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 0.88 (59748 hom., cov: 30)
  • Exomes 𝑓: 0.85 (377502 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-19-61A>G		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-61A>G		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.-19-61A>G		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.-19-61A>G		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-19-61A>G		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-61A>G		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-19-61A>G		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-19-61A>G		intron_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134340 AN: 152028 Hom.: 59685 Cov.: 30

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.854

GnomAD4 exome AF: 0.849 AC: 885873 AN: 1043536 Hom.: 377502 AF XY: 0.844 AC XY: 451671 AN XY: 535018

Gnomad4 AFR exome AF: 0.975

Gnomad4 AMR exome AF: 0.906

Gnomad4 ASJ exome AF: 0.807

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.768

Gnomad4 FIN exome AF: 0.892

Gnomad4 NFE exome AF: 0.849

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.884 AC: 134465 AN: 152146 Hom.: 59748 Cov.: 30 AF XY: 0.883 AC XY: 65688 AN XY: 74388

Gnomad4 AFR AF: 0.972

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.854

Alfa AF: 0.845 Hom.: 3864

Bravo AF: 0.890

Asia WGS AF: 0.839 AC: 2913 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	1.4
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: rs2143404; hg19: chr6-35610681;