rs368867118

Variant names:

• chr7-30019131-G-A
• rs368867118
• NM_017946.4:c.350-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-30019131-G-A
• chr7-30019131-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_017946.4(FKBP14):​c.350-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000487 in 1,561,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: FKBP14 NM_017946.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002219
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.114
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-30019131-G-A is Benign according to our data. Variant chr7-30019131-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 473002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.350-8C>T		splice_region intron	N/A	NP_060416.1	Q9NWM8
	FKBP14	NR_046478.2		n.636-8C>T		splice_region intron	N/A
	FKBP14	NR_046479.2		n.392-8C>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.350-8C>T		splice_region intron	N/A	ENSP00000222803.5	Q9NWM8
	FKBP14	ENST00000419018.1	TSL:1	n.198-8C>T		splice_region intron	N/A	ENSP00000406270.1	F8WBZ0
	FKBP14	ENST00000412494.1	TSL:2	n.*85-8C>T		splice_region intron	N/A	ENSP00000403279.1	H7C1Z9

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000894

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000508 AC: 10 AN: 196772 AF XY: 0.0000552

Gnomad AFR exome AF: 0.000733

Gnomad AMR exome AF: 0.0000499

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000255 AC: 36 AN: 1409124 Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 19 AN XY: 700710

African (AFR) AF: 0.00109 AC: 32 AN: 29228

American (AMR) AF: 0.0000670 AC: 2 AN: 29854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24536

East Asian (EAS) AF: 0.00 AC: 0 AN: 36120

South Asian (SAS) AF: 0.00 AC: 0 AN: 77126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52754

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5636

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095808

Other (OTH) AF: 0.0000172 AC: 1 AN: 58062

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20 AN XY: 74430

African (AFR) AF: 0.000891 AC: 37 AN: 41528

American (AMR) AF: 0.000196 AC: 3 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000272

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (1)
-	-	1	FKBP14-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0020
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: rs368867118; hg19: chr7-30058747;