rs564626031

Variant names:

• chr7-30026458-CAAA-C
• rs564626031
• NM_017946.4:c.48_50delTTT

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The NM_017946.4(FKBP14):​c.48_50delTTT​(p.Leu17del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,614,034 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: FKBP14 NM_017946.4 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.486
• Publications: 0 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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_017946.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 7-30026458-CAAA-C is Benign according to our data. Variant chr7-30026458-CAAA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 374451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000112 (17/152318) while in subpopulation SAS AF = 0.0029 (14/4826). AF 95% confidence interval is 0.00175. There are 0 homozygotes in GnomAd4. There are 15 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	NM_017946.4	MANE Select	c.48_50delTTT	p.Leu17del	disruptive_inframe_deletion	Exon 1 of 4	NP_060416.1	Q9NWM8
	FKBP14	NR_046478.2		n.242_244delTTT		non_coding_transcript_exon	Exon 1 of 5
	FKBP14	NR_046479.2		n.242_244delTTT		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.48_50delTTT	p.Leu17del	disruptive_inframe_deletion	Exon 1 of 4	ENSP00000222803.5	Q9NWM8
	FKBP14	ENST00000419018.1	TSL:1	n.48_50delTTT		non_coding_transcript_exon	Exon 1 of 3	ENSP00000406270.1	F8WBZ0
	FKBP14	ENST00000479939.1	TSL:1	n.176_178delTTT		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000438 AC: 110 AN: 251402 AF XY: 0.000603

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000246 AC: 360 AN: 1461716 Hom.: 2 AF XY: 0.000341 AC XY: 248 AN XY: 727166

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.000179 AC: 8 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00362 AC: 312 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5734

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111918

Other (OTH) AF: 0.000215 AC: 13 AN: 60376

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000491

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=58/42	polymorphism

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: rs564626031; hg19: chr7-30066074;