rs10947564

Variant names:

• chr6-35688197-T-C
• rs10947564
• NM_004117.4:c.-20+607A>G

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+607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,176 control chromosomes in the GnomAD database, including 2,405 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 0.17 (2405 hom., cov: 33)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-20+607A>G		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-20+32131A>G		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-20+535A>G		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-20+607A>G		intron_variant	Intron 1 of 6		NP_001139249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP5	ENST00000357266.9	c.-20+607A>G		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-20+32131A>G		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-20+535A>G		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-20+607A>G		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26463 AN: 152060 Hom.: 2404 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.174 AC: 26471 AN: 152176 Hom.: 2405 Cov.: 33 AF XY: 0.179 AC XY: 13347 AN XY: 74406

African (AFR) AF: 0.166 AC: 6906 AN: 41540

American (AMR) AF: 0.160 AC: 2454 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1891 AN: 5152

South Asian (SAS) AF: 0.225 AC: 1089 AN: 4832

European-Finnish (FIN) AF: 0.183 AC: 1936 AN: 10608

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11164 AN: 67962

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.168 Hom.: 527

Bravo AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.60
PhyloP100		0.49
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: rs10947564; hg19: chr6-35655974;