chr6-35661423-A-C

Variant names:

• chr6-35661423-A-C
• rs7747647
• NM_004117.4:c.-19-18580T>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.-19-18580T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.25 (8776 hom., cov: 12)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• 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 = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP5	NM_004117.4	c.-19-18580T>G		intron_variant	Intron 1 of 10	ENST00000357266.9	NP_004108.1
FKBP5	NM_001145775.3	c.-19-18580T>G		intron_variant	Intron 2 of 11		NP_001139247.1
FKBP5	NM_001145776.2	c.-19-18580T>G		intron_variant	Intron 1 of 10		NP_001139248.1
FKBP5	NM_001145777.2	c.-19-18580T>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.-19-18580T>G		intron_variant	Intron 1 of 10	1	NM_004117.4	ENSP00000349811.3
FKBP5	ENST00000536438.5	c.-19-18580T>G		intron_variant	Intron 2 of 11	1		ENSP00000444810.1
FKBP5	ENST00000539068.5	c.-19-18580T>G		intron_variant	Intron 1 of 10	1		ENSP00000441205.1
FKBP5	ENST00000542713.1	c.-19-18580T>G		intron_variant	Intron 1 of 6	2		ENSP00000442340.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 20707 AN: 83536 Hom.: 8742 Cov.: 12

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.249 AC: 20781 AN: 83618 Hom.: 8776 Cov.: 12 AF XY: 0.250 AC XY: 9957 AN XY: 39904

African (AFR) AF: 0.561 AC: 15026 AN: 26792

American (AMR) AF: 0.190 AC: 1522 AN: 7990

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 365 AN: 1586

East Asian (EAS) AF: 0.163 AC: 425 AN: 2602

South Asian (SAS) AF: 0.0267 AC: 64 AN: 2394

European-Finnish (FIN) AF: 0.0521 AC: 200 AN: 3838

Middle Eastern (MID) AF: 0.227 AC: 39 AN: 172

European-Non Finnish (NFE) AF: 0.0764 AC: 2803 AN: 36666

Other (OTH) AF: 0.236 AC: 265 AN: 1122

Alfa AF: 0.178 Hom.: 732

Asia WGS AF: 0.129 AC: 249 AN: 1950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		-0.47
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: rs7747647; hg19: chr6-35629200;