NM_017946.4:c.*672C>T

Variant names:

• chr7-30014063-G-A
• rs3793247
• NM_017946.4:c.*672C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017946.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	NM_017946.4	MANE Select	c.*672C>T		3_prime_UTR	Exon 4 of 4	NP_060416.1
	FKBP14	NR_046478.2		n.1594C>T		non_coding_transcript_exon	Exon 5 of 5
	FKBP14	NR_046479.2		n.1350C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.*672C>T		3_prime_UTR	Exon 4 of 4	ENSP00000222803.5
	FKBP14-AS1	ENST00000419103.1	TSL:4	n.344+5686G>A		intron	N/A
	FKBP14-AS1	ENST00000422239.6	TSL:5	n.679+5686G>A		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.115 AC: 3 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

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: 66 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10869 AN: 67932

Other (OTH) AF: 0.177 AC: 373 AN: 2110

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.92
DANN	Benign	0.46
PhyloP100		-0.89
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: rs3793247; hg19: chr7-30053679;