rs7771722

Variant names:

• chr6-35646221-G-A
• rs7771722
• NM_004117.4:c.-19-3378C>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.-19-3378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,282 control chromosomes in the GnomAD database, including 213 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 0.043 (213 hom., cov: 32)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-19-3378C>T		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-3378C>T		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-19-3378C>T		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-19-3378C>T		intron_variant	Intron 1 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-19-3378C>T		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-3378C>T		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-19-3378C>T		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-19-3378C>T		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6509 AN: 152164 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0415

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

GnomAD4 genome AF: 0.0428 AC: 6514 AN: 152282 Hom.: 213 Cov.: 32 AF XY: 0.0414 AC XY: 3082 AN XY: 74458

African (AFR) AF: 0.0926 AC: 3846 AN: 41546

American (AMR) AF: 0.0299 AC: 457 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4822

European-Finnish (FIN) AF: 0.0131 AC: 139 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0247 AC: 1681 AN: 68034

Other (OTH) AF: 0.0411 AC: 87 AN: 2116

Alfa AF: 0.0322 Hom.: 15

Bravo AF: 0.0462

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.62
PhyloP100		-0.27
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

Other links and lift over

dbSNP: rs7771722; hg19: chr6-35613998;