rs17150692

chr7-30026344-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017946.4(FKBP14):c.165C>T(p.Tyr55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,612,990 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (47 hom., cov: 33)
  • Exomes 𝑓: 0.018 (357 hom.)
• Consequence: FKBP14 NM_017946.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.81

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

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 7-30026344-G-A is Benign according to our data. Variant chr7-30026344-G-A is described in ClinVar as [Benign]. Clinvar id is 384694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-30026344-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP14	NM_017946.4	c.165C>T	p.Tyr55=	synonymous_variant	1/4	ENST00000222803.10
FKBP14	XM_047420550.1	c.165C>T	p.Tyr55=	synonymous_variant	1/4
FKBP14	NR_046478.2	n.359C>T		non_coding_transcript_exon_variant	1/5
FKBP14	NR_046479.2	n.359C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP14	ENST00000222803.10	c.165C>T	p.Tyr55=	synonymous_variant	1/4	1	NM_017946.4	P1
FKBP14-AS1	ENST00000422239.6	n.1637G>A		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2954 AN: 152182 Hom.: 46 Cov.: 33

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0245 AC: 6149 AN: 250820 Hom.: 134 AF XY: 0.0229 AC XY: 3111 AN XY: 135616

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.0616

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.0374

Gnomad SAS exome AF: 0.0215

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.0163

Gnomad OTH exome AF: 0.0229

GnomAD4 exome AF: 0.0185 AC: 27013 AN: 1460690 Hom.: 357 Cov.: 31 AF XY: 0.0183 AC XY: 13273 AN XY: 726726

Gnomad4 AFR exome AF: 0.0192

Gnomad4 AMR exome AF: 0.0596

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.0444

Gnomad4 SAS exome AF: 0.0207

Gnomad4 FIN exome AF: 0.00212

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0209

GnomAD4 genome AF: 0.0194 AC: 2955 AN: 152300 Hom.: 47 Cov.: 33 AF XY: 0.0191 AC XY: 1425 AN XY: 74458

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0191 Hom.: 41

Bravo AF: 0.0232

Asia WGS AF: 0.0250 AC: 85 AN: 3478

EpiCase AF: 0.0166

EpiControl AF: 0.0198

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 07, 2016

- -

Ehlers-Danlos syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 16, 2022

- -

Ehlers-Danlos syndrome, kyphoscoliotic type, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Cardiovascular phenotype Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	17
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs17150692; hg19: chr7-30065960; COSMIC: COSV51651230; COSMIC: COSV51651230;