chr6-35720842-T-C

Variant names:

• chr6-35720842-T-C
• rs2817032
• ENST00000536438.5:c.-240-294A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000536438.5(FKBP5):​c.-240-294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,146 control chromosomes in the GnomAD database, including 4,871 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 0.24 (4871 hom., cov: 32)
• Consequence: FKBP5 ENST00000536438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_001145775.3	c.-240-294A>G		intron_variant	Intron 1 of 11		NP_001139247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000536438.5	c.-240-294A>G		intron_variant	Intron 1 of 11	1		ENSP00000444810.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36603 AN: 152028 Hom.: 4864 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.241 AC: 36628 AN: 152146 Hom.: 4871 Cov.: 32 AF XY: 0.243 AC XY: 18078 AN XY: 74386

African (AFR) AF: 0.119 AC: 4951 AN: 41508

American (AMR) AF: 0.279 AC: 4267 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1245 AN: 5186

South Asian (SAS) AF: 0.374 AC: 1802 AN: 4820

European-Finnish (FIN) AF: 0.264 AC: 2796 AN: 10578

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19630 AN: 67980

Other (OTH) AF: 0.256 AC: 540 AN: 2112

Alfa AF: 0.270 Hom.: 9961

Bravo AF: 0.234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.39
DANN	Benign	0.82
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2817032; hg19: chr6-35688619;