7-30019116-A-G

Variant names:

• chr7-30019116-A-G
• rs202182643
• NM_017946.4:c.357T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017946.4(FKBP14):​c.357T>C​(p.Ile119Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FKBP14 NM_017946.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.465 with no splicing effect.

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.357T>C	p.Ile119Ile	synonymous	Exon 3 of 4	NP_060416.1
	FKBP14	NR_046478.2		n.643T>C		non_coding_transcript_exon	Exon 4 of 5
	FKBP14	NR_046479.2		n.399T>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.357T>C	p.Ile119Ile	synonymous	Exon 3 of 4	ENSP00000222803.5
	FKBP14	ENST00000419018.1	TSL:1	n.*4T>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000406270.1
	FKBP14	ENST00000419018.1	TSL:1	n.*4T>C		3_prime_UTR	Exon 2 of 3	ENSP00000406270.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418118 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705008

African (AFR) AF: 0.00 AC: 0 AN: 30008

American (AMR) AF: 0.00 AC: 0 AN: 32618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24856

East Asian (EAS) AF: 0.00 AC: 0 AN: 36604

South Asian (SAS) AF: 0.00 AC: 0 AN: 78348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098558

Other (OTH) AF: 0.00 AC: 0 AN: 58520

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs202182643; hg19: chr7-30058732;