chr7-30022684-G-A

Variant names:

• chr7-30022684-G-A
• rs148034796
• NM_017946.4:c.330C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_017946.4(FKBP14):​c.330C>T​(p.Gly110Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,613,596 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: FKBP14 NM_017946.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.299
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-30022684-G-A is Benign according to our data. Variant chr7-30022684-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 390200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.299 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00161 (245/152138) while in subpopulation AFR AF = 0.00566 (235/41500). AF 95% confidence interval is 0.00507. There are 0 homozygotes in GnomAd4. There are 108 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.330C>T	p.Gly110Gly	synonymous	Exon 2 of 4	NP_060416.1	Q9NWM8
	FKBP14	NR_046478.2		n.524C>T		non_coding_transcript_exon	Exon 2 of 5
	FKBP14	NR_046479.2		n.392-3561C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP14	ENST00000222803.10	TSL:1 MANE Select	c.330C>T	p.Gly110Gly	synonymous	Exon 2 of 4	ENSP00000222803.5	Q9NWM8
	FKBP14	ENST00000479939.1	TSL:1	n.458C>T		non_coding_transcript_exon	Exon 2 of 2
	FKBP14	ENST00000419018.1	TSL:1	n.198-3561C>T		intron	N/A	ENSP00000406270.1	F8WBZ0

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 244 AN: 152022 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00565

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

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: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000378 AC: 95 AN: 250992 AF XY: 0.000243

Gnomad AFR exome AF: 0.00554

Gnomad AMR exome AF: 0.000116

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: 0.000163

GnomAD4 exome AF: 0.000168 AC: 245 AN: 1461458 Hom.: 1 Cov.: 31 AF XY: 0.000139 AC XY: 101 AN XY: 727032

African (AFR) AF: 0.00616 AC: 206 AN: 33458

American (AMR) AF: 0.000179 AC: 8 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111832

Other (OTH) AF: 0.000464 AC: 28 AN: 60368

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152138 Hom.: 0 Cov.: 33 AF XY: 0.00145 AC XY: 108 AN XY: 74372

African (AFR) AF: 0.00566 AC: 235 AN: 41500

American (AMR) AF: 0.000327 AC: 5 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000673 Hom.: 0

Bravo AF: 0.00159

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.7
DANN	Benign	0.71
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs148034796; hg19: chr7-30062300;