chr6-35640178-C-T

Position:

• chr6-35640178-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004117.4(FKBP5):​c.105+2542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 152,292 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.036 (130 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 6-35640178-C-T is Benign according to our data. Variant chr6-35640178-C-T is described in ClinVar as [Benign]. Clinvar id is 1179585.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.105+2542G>A		intron_variant		ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.105+2542G>A		intron_variant			NP_001139247.1
FKBP5	NM_001145776.2	c.105+2542G>A		intron_variant			NP_001139248.1
FKBP5	NM_001145777.2	c.105+2542G>A		intron_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.105+2542G>A		intron_variant		1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.105+2542G>A		intron_variant		1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.105+2542G>A		intron_variant		1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.105+2542G>A		intron_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5452 AN: 152174 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0358 AC: 5458 AN: 152292 Hom.: 130 Cov.: 32 AF XY: 0.0346 AC XY: 2579 AN XY: 74484

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0284 Hom.: 8

Bravo AF: 0.0383

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

This variant is associated with the following publications: (PMID: 23936393) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.66

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: rs73748206; hg19: chr6-35607955;