Genetic Variant FKBP7:p.Arg185His (chr2-178465885-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181342.3(FKBP7):c.554G>A(p.Arg185His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,607,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

FKBP7
NM_181342.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00800

Publications

6 publications found

Variant links:

Genes affected

FKBP7 (HGNC:3723): (FKBP prolyl isomerase 7) The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. Members of this family exhibit PPIase activity and function as molecular chaperones. A similar protein in mouse is located in the endoplasmic reticulum and binds calcium. [provided by RefSeq, Jul 2008]

FKBP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042203933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181342.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FKBP7	NM_181342.3	MANE Select	c.554G>A	p.Arg185His	missense	Exon 4 of 4	NP_851939.1	Q9Y680-2
FKBP7	NM_001135212.2		c.551G>A	p.Arg184His	missense	Exon 4 of 4	NP_001128684.1	Q9Y680-3
FKBP7	NM_001410972.1		c.*18G>A		3_prime_UTR	Exon 3 of 3	NP_001397901.1	B4DRE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FKBP7	ENST00000424785.7	TSL:1 MANE Select	c.554G>A	p.Arg185His	missense	Exon 4 of 4	ENSP00000413152.2	Q9Y680-2
FKBP7	ENST00000434643.6	TSL:1	c.551G>A	p.Arg184His	missense	Exon 4 of 4	ENSP00000415486.2	Q9Y680-3
FKBP7	ENST00000233092.10	TSL:1	n.*284G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000233092.6	Q9Y680-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000982

AC:

AN:

244454

AF XY:

0.0000833

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000155

AC:

225

AN:

1455270

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

723700

show subpopulations

African (AFR)

AF:

0.0000603

AC:

AN:

33150

American (AMR)

AF:

0.000207

AC:

AN:

43424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.0000507

AC:

AN:

39416

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84458

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.000185

AC:

205

AN:

1109726

Other (OTH)

AF:

0.0000832

AC:

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41548

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000894

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.74

M_CAP

Benign

0.018

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.97

PhyloP100

0.0080

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Benign

0.16

Polyphen

0.12

Vest4

0.13

MVP

0.28

MPC

0.084

ClinPred

0.13

GERP RS

2.0

Varity_R

0.032

gMVP

0.52

Mutation Taster

=81/19

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over