NM_004117.4:c.-19-61A>G

Variant names:

• chr6-35642904-T-C
• rs2143404
• NM_004117.4:c.-19-61A>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.-19-61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 1,195,682 control chromosomes in the GnomAD database, including 437,250 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 0.88 (59748 hom., cov: 30)
  • Exomes 𝑓: 0.85 (377502 hom.)
• Consequence: FKBP5 NM_004117.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.964 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.-19-61A>G		intron	N/A	NP_004108.1	Q13451-1
	FKBP5	NM_001145775.3		c.-19-61A>G		intron	N/A	NP_001139247.1	Q13451-1
	FKBP5	NM_001145776.2		c.-19-61A>G		intron	N/A	NP_001139248.1	Q13451-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.-19-61A>G		intron	N/A	ENSP00000349811.3	Q13451-1
	FKBP5	ENST00000536438.5	TSL:1	c.-19-61A>G		intron	N/A	ENSP00000444810.1	Q13451-1
	FKBP5	ENST00000539068.5	TSL:1	c.-19-61A>G		intron	N/A	ENSP00000441205.1	Q13451-1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134340 AN: 152028 Hom.: 59685 Cov.: 30

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.854

GnomAD4 exome AF: 0.849 AC: 885873 AN: 1043536 Hom.: 377502 AF XY: 0.844 AC XY: 451671 AN XY: 535018

African (AFR) AF: 0.975 AC: 24061 AN: 24668

American (AMR) AF: 0.906 AC: 35362 AN: 39010

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 17198 AN: 21316

East Asian (EAS) AF: 0.844 AC: 31341 AN: 37144

South Asian (SAS) AF: 0.768 AC: 55554 AN: 72298

European-Finnish (FIN) AF: 0.892 AC: 38250 AN: 42864

Middle Eastern (MID) AF: 0.784 AC: 3668 AN: 4676

European-Non Finnish (NFE) AF: 0.849 AC: 641189 AN: 755266

Other (OTH) AF: 0.848 AC: 39250 AN: 46294

GnomAD4 genome AF: 0.884 AC: 134465 AN: 152146 Hom.: 59748 Cov.: 30 AF XY: 0.883 AC XY: 65688 AN XY: 74388

African (AFR) AF: 0.972 AC: 40370 AN: 41532

American (AMR) AF: 0.880 AC: 13432 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2827 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4386 AN: 5152

South Asian (SAS) AF: 0.757 AC: 3646 AN: 4814

European-Finnish (FIN) AF: 0.900 AC: 9525 AN: 10588

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57489 AN: 67998

Other (OTH) AF: 0.854 AC: 1807 AN: 2116

Alfa AF: 0.853 Hom.: 4220

Bravo AF: 0.890

Asia WGS AF: 0.839 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-1.7
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: rs2143404; hg19: chr6-35610681;