rs3793247

chr7-30014063-G-Achr7-30014063-G-Cchr7-30014063-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886

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 -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 id 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/exons	MANE	UniProt
FKBP14	NM_017946.4	c.*672C>T		3_prime_UTR_variant	4/4	ENST00000222803.10
FKBP14	XM_047420550.1	c.477+4933C>T		intron_variant
FKBP14	NR_046478.2	n.1594C>T		non_coding_transcript_exon_variant	5/5
FKBP14	NR_046479.2	n.1350C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP14	ENST00000222803.10	c.*672C>T		3_prime_UTR_variant	4/4	1	NM_017946.4	P1
FKBP14-AS1	ENST00000422239.6	n.679+5686G>A		intron_variant, non_coding_transcript_variant		5
FKBP14-AS1	ENST00000419103.1	n.344+5686G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27298 AN: 151686 Hom.: 2585 Cov.: 31

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: 3 AN: 28 Hom.: 1 Cov.: 0 AF XY: 0.107 AC XY: 3 AN XY: 28

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.180 AC: 27335 AN: 151804 Hom.: 2597 Cov.: 31 AF XY: 0.178 AC XY: 13208 AN XY: 74172

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0748

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.177

Alfa AF: 0.0800 Hom.: 92

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

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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
Dann	Benign	0.46

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: rs3793247; hg19: chr7-30053679;