rs41270080

Variant names:

• chr6-35574268-C-A
• rs41270080
• NM_004117.4:c.*1567G>T

Variant summary

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

The NM_004117.4(FKBP5):​c.*1567G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 152,050 control chromosomes in the GnomAD database, including 787 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 0.072 (787 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: FKBP5 NM_004117.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 10 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]

LINC03135 (HGNC:58100):

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 (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004117.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_004117.4	MANE Select	c.*1567G>T		3_prime_UTR	Exon 11 of 11	NP_004108.1	Q13451-1
	FKBP5	NM_001145775.3		c.*1567G>T		3_prime_UTR	Exon 12 of 12	NP_001139247.1	Q13451-1
	FKBP5	NM_001145776.2		c.*1567G>T		3_prime_UTR	Exon 11 of 11	NP_001139248.1	Q13451-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.*1567G>T		3_prime_UTR	Exon 11 of 11	ENSP00000349811.3	Q13451-1
	FKBP5	ENST00000536438.5	TSL:1	c.*1567G>T		3_prime_UTR	Exon 12 of 12	ENSP00000444810.1	Q13451-1
	FKBP5	ENST00000539068.5	TSL:1	c.*1567G>T		3_prime_UTR	Exon 11 of 11	ENSP00000441205.1	Q13451-1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10929 AN: 151932 Hom.: 783 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00583

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0694

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0721 AC: 10959 AN: 152050 Hom.: 787 Cov.: 33 AF XY: 0.0706 AC XY: 5248 AN XY: 74332

African (AFR) AF: 0.194 AC: 8064 AN: 41462

American (AMR) AF: 0.0405 AC: 618 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.00562 AC: 27 AN: 4800

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10578

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0248 AC: 1684 AN: 67972

Other (OTH) AF: 0.0687 AC: 145 AN: 2110

Alfa AF: 0.0444 Hom.: 120

Bravo AF: 0.0795

Asia WGS AF: 0.0140 AC: 47 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.44
PhyloP100		-0.043
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41270080;

hg19: chr6-35542045;