dbSNP rs3793247: FKBP14:c.*672C>T (chr7-30014063-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_017946.4(FKBP14):c.*672C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,832 control chromosomes in the GnomAD database, including 2,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2597 hom., cov: 31)

Exomes 𝑓: 0.11 ( 1 hom. )

Consequence

FKBP14
NM_017946.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.886

Publications

5 publications found

Variant links:

Genes affected

FKBP14 (HGNC:18625): (FKBP prolyl isomerase 14) The protein encoded by this gene is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases. The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding. Defects in this gene are a cause of a type of Ehlers-Danlos syndrome (EDS). Both a protein-coding variant and noncoding variants are transcribed from this gene. [provided by RefSeq, Mar 2012]

FKBP14 links:

FKBP14-AS1 (HGNC:40990): (FKBP14 antisense RNA 1)

FKBP14-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 7-30014063-G-A is Benign according to our data. Variant chr7-30014063-G-A is described in ClinVar as Benign. ClinVar VariationId is 402867.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP14	NM_017946.4 link	c.*672C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000222803.10	NP_060416.1	Q9NWM8A0A090N7V8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FKBP14	ENST00000222803.10 link	c.*672C>T	3_prime_UTR_variant	Exon 4 of 4	1	NM_017946.4	ENSP00000222803.5	Q9NWM8
FKBP14-AS1	ENST00000419103.1 link	n.344+5686G>A	intron_variant	Intron 2 of 2	4
FKBP14-AS1	ENST00000422239.6 link	n.679+5686G>A	intron_variant	Intron 3 of 3	5
FKBP14	ENST00000419018.1 link	n.*955C>T	downstream_gene_variant		1		ENSP00000406270.1	F8WBZ0

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27298

AN:

151686

Hom.:

2585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.0747

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.107

AC:

AN:

Hom.:

Cov.:

AF XY:

0.107

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.115

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.180

AC:

27335

AN:

151804

Hom.:

2597

Cov.:

AF XY:

0.178

AC XY:

13208

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.241

AC:

9956

AN:

41372

American (AMR)

AF:

0.169

AC:

2577

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

721

AN:

3466

East Asian (EAS)

AF:

0.0748

AC:

384

AN:

5132

South Asian (SAS)

AF:

0.139

AC:

667

AN:

4800

European-Finnish (FIN)

AF:

0.149

AC:

1568

AN:

10542

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10869

AN:

67932

Other (OTH)

AF:

0.177

AC:

373

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1135

2271

3406

4542

5677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.0870

Hom.:

106

Bravo

AF:

0.184

Asia WGS

AF:

0.112

AC:

392

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.92

(source)

DANN

Benign

0.46

PhyloP100

-0.89

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over