rs7747121

Variant names:

• chr6-35626206-A-G
• rs7747121
• NM_004117.4:c.251-5932T>C

Variant summary

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

The NM_004117.4(FKBP5):​c.251-5932T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,242 control chromosomes in the GnomAD database, including 1,178 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 0.084 (1178 hom., cov: 31)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 3 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 = 0.231 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.251-5932T>C		intron	N/A	NP_004108.1
	FKBP5	NM_001145775.3		c.251-5932T>C		intron	N/A	NP_001139247.1
	FKBP5	NM_001145776.2		c.251-5932T>C		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.251-5932T>C		intron	N/A	ENSP00000349811.3
	FKBP5	ENST00000536438.5	TSL:1	c.251-5932T>C		intron	N/A	ENSP00000444810.1
	FKBP5	ENST00000539068.5	TSL:1	c.251-5932T>C		intron	N/A	ENSP00000441205.1

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12804 AN: 152124 Hom.: 1166 Cov.: 31

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00682

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0801

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

GnomAD4 genome AF: 0.0844 AC: 12855 AN: 152242 Hom.: 1178 Cov.: 31 AF XY: 0.0828 AC XY: 6168 AN XY: 74456

African (AFR) AF: 0.235 AC: 9755 AN: 41504

American (AMR) AF: 0.0476 AC: 728 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 223 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.00662 AC: 32 AN: 4834

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1738 AN: 68032

Other (OTH) AF: 0.0792 AC: 167 AN: 2108

Alfa AF: 0.0642 Hom.: 114

Bravo AF: 0.0935

Asia WGS AF: 0.0180 AC: 62 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.75
PhyloP100		-0.34
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: rs7747121; hg19: chr6-35593983;