NM_004117.4:c.841-1672G>A

Variant names:

• chr6-35581893-C-T
• rs755658
• NM_004117.4:c.841-1672G>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.841-1672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 985,458 control chromosomes in the GnomAD database, including 4,311 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 0.066 (480 hom., cov: 32)
  • Exomes 𝑓: 0.095 (3831 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.112 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.841-1672G>A		intron	N/A	NP_004108.1
	FKBP5	NM_001145777.2		c.*5083G>A		3_prime_UTR	Exon 7 of 7	NP_001139249.1
	FKBP5	NM_001145775.3		c.841-1672G>A		intron	N/A	NP_001139247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.841-1672G>A		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.841-1672G>A		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.841-1672G>A		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10077 AN: 152132 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.0636

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0950 AC: 79147 AN: 833208 Hom.: 3831 Cov.: 33 AF XY: 0.0949 AC XY: 36513 AN XY: 384794

African (AFR) AF: 0.00962 AC: 152 AN: 15794

American (AMR) AF: 0.125 AC: 123 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 108 AN: 5152

East Asian (EAS) AF: 0.0705 AC: 256 AN: 3632

South Asian (SAS) AF: 0.0621 AC: 1022 AN: 16462

European-Finnish (FIN) AF: 0.0536 AC: 15 AN: 280

Middle Eastern (MID) AF: 0.0327 AC: 53 AN: 1622

European-Non Finnish (NFE) AF: 0.0986 AC: 75122 AN: 761982

Other (OTH) AF: 0.0841 AC: 2296 AN: 27300

GnomAD4 genome AF: 0.0662 AC: 10074 AN: 152250 Hom.: 480 Cov.: 32 AF XY: 0.0634 AC XY: 4720 AN XY: 74436

African (AFR) AF: 0.0184 AC: 765 AN: 41554

American (AMR) AF: 0.116 AC: 1779 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3472

East Asian (EAS) AF: 0.0634 AC: 328 AN: 5176

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4826

European-Finnish (FIN) AF: 0.0418 AC: 444 AN: 10614

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0918 AC: 6244 AN: 68004

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0864 Hom.: 460

Bravo AF: 0.0710

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.52
PhyloP100		-0.36
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: rs755658; hg19: chr6-35549670;