rs737054

Variant names:

• chr6-35607710-G-A
• rs737054
• NM_004117.4:c.509-10306C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-35607710-G-A
• chr6-35607710-G-C
• chr6-35607710-G-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.509-10306C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 163,258 control chromosomes in the GnomAD database, including 4,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (4211 hom., cov: 31)
  • Exomes 𝑓: 0.26 (433 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: 0.757
• Publications: 22 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]

RPL36P9 (HGNC:36746): (ribosomal protein L36 pseudogene 9)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 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.509-10306C>T		intron	N/A	NP_004108.1	Q13451-1
	FKBP5	NM_001145775.3		c.509-10306C>T		intron	N/A	NP_001139247.1	Q13451-1
	FKBP5	NM_001145776.2		c.509-10306C>T		intron	N/A	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.509-10306C>T		intron	N/A	ENSP00000349811.3	Q13451-1
	FKBP5	ENST00000536438.5	TSL:1	c.509-10306C>T		intron	N/A	ENSP00000444810.1	Q13451-1
	FKBP5	ENST00000539068.5	TSL:1	c.509-10306C>T		intron	N/A	ENSP00000441205.1	Q13451-1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32717 AN: 151908 Hom.: 4202 Cov.: 31

Gnomad AFR AF: 0.0761

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.265 AC: 2973 AN: 11232 Hom.: 433 Cov.: 0 AF XY: 0.265 AC XY: 1677 AN XY: 6338

African (AFR) AF: 0.0549 AC: 9 AN: 164

American (AMR) AF: 0.419 AC: 161 AN: 384

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 15 AN: 54

East Asian (EAS) AF: 0.305 AC: 89 AN: 292

South Asian (SAS) AF: 0.170 AC: 201 AN: 1180

European-Finnish (FIN) AF: 0.277 AC: 1390 AN: 5014

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.266 AC: 998 AN: 3758

Other (OTH) AF: 0.287 AC: 109 AN: 380

GnomAD4 genome AF: 0.215 AC: 32734 AN: 152026 Hom.: 4211 Cov.: 31 AF XY: 0.214 AC XY: 15891 AN XY: 74286

African (AFR) AF: 0.0760 AC: 3154 AN: 41512

American (AMR) AF: 0.301 AC: 4589 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3468

East Asian (EAS) AF: 0.233 AC: 1202 AN: 5148

South Asian (SAS) AF: 0.157 AC: 751 AN: 4796

European-Finnish (FIN) AF: 0.273 AC: 2889 AN: 10572

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18318 AN: 67948

Other (OTH) AF: 0.252 AC: 531 AN: 2106

Alfa AF: 0.263 Hom.: 9949

Bravo AF: 0.216

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely risk allele

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Susceptibility to severe depressive disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.78
DANN	Benign	0.60
PhyloP100		0.76
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: rs737054; hg19: chr6-35575487;