rs7757037

Variant names:

• chr6-35580459-G-A
• rs7757037
• NM_004117.4:c.841-238C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-35580459-G-A
• chr6-35580459-G-C
• chr6-35580459-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004117.4(FKBP5):​c.841-238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 373,696 control chromosomes in the GnomAD database, including 43,104 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 0.45 (15525 hom., cov: 28)
  • Exomes 𝑓: 0.50 (27579 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.841-238C>T		intron_variant	Intron 8 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.841-238C>T		intron_variant	Intron 9 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.841-238C>T		intron_variant	Intron 8 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.*6517C>T		downstream_gene_variant			NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.841-238C>T		intron_variant	Intron 8 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.841-238C>T		intron_variant	Intron 9 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.841-238C>T		intron_variant	Intron 8 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.*6517C>T		downstream_gene_variant		2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 67782 AN: 149706 Hom.: 15519 Cov.: 28

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.496 AC: 110938 AN: 223888 Hom.: 27579 AF XY: 0.495 AC XY: 56735 AN XY: 114620

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.552

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.453 AC: 67805 AN: 149808 Hom.: 15525 Cov.: 28 AF XY: 0.455 AC XY: 33214 AN XY: 72958

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.456

Alfa AF: 0.473 Hom.: 25442

Bravo AF: 0.451

Asia WGS AF: 0.496 AC: 1720 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	0.88
DANN	Benign	0.61

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: rs7757037; hg19: chr6-35548236;