NM_004117.4:c.-20+150G>A

Variant names:

• chr6-35688654-C-T
• rs13215797
• NM_004117.4:c.-20+150G>A

Variant summary

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

The NM_004117.4(FKBP5):​c.-20+150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 150,722 control chromosomes in the GnomAD database, including 1,284 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 0.11 (1282 hom., cov: 33)
  • Exomes 𝑓: 0.34 (2 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.213 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_004117.4	MANE Select	c.-20+150G>A		intron	N/A	NP_004108.1
	FKBP5	NM_001145775.3		c.-20+31674G>A		intron	N/A	NP_001139247.1
	FKBP5	NM_001145776.2		c.-20+78G>A		intron	N/A	NP_001139248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.-20+150G>A		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.-20+31674G>A		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.-20+78G>A		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16762 AN: 150582 Hom.: 1277 Cov.: 33

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.344 AC: 11 AN: 32 Hom.: 2 AF XY: 0.333 AC XY: 10 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

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) AF: 0.321 AC: 9 AN: 28

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.111 AC: 16783 AN: 150690 Hom.: 1282 Cov.: 33 AF XY: 0.113 AC XY: 8301 AN XY: 73618

African (AFR) AF: 0.0238 AC: 985 AN: 41384

American (AMR) AF: 0.219 AC: 3315 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3454

East Asian (EAS) AF: 0.206 AC: 1047 AN: 5092

South Asian (SAS) AF: 0.121 AC: 583 AN: 4828

European-Finnish (FIN) AF: 0.128 AC: 1287 AN: 10050

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.128 AC: 8634 AN: 67446

Other (OTH) AF: 0.157 AC: 327 AN: 2088

Alfa AF: 0.117 Hom.: 166

Bravo AF: 0.119

Asia WGS AF: 0.180 AC: 594 AN: 3310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		-0.47
PromoterAI		-0.092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13215797; hg19: chr6-35656431;