rs2233913

Variant names:

• chr9-113220936-T-C
• rs2233913
• NM_015258.2:c.53+255A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015258.2(FKBP15):​c.53+255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,078 control chromosomes in the GnomAD database, including 1,240 homozygotes. 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: 𝑓 0.11 (1240 hom., cov: 32)
• Consequence: FKBP15 NM_015258.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

Genes affected

FKBP15 (HGNC:23397): (FKBP prolyl isomerase family member 15) Predicted to enable actin binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in endocytosis and protein peptidyl-prolyl isomerization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKBP15	NM_015258.2	c.53+255A>G		intron_variant	Intron 1 of 27	ENST00000238256.8	NP_056073.1
FKBP15	XM_006717018.3	c.53+255A>G		intron_variant	Intron 1 of 27		XP_006717081.1
FKBP15	XM_006717019.2	c.-36+255A>G		intron_variant	Intron 1 of 26		XP_006717082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP15	ENST00000238256.8	c.53+255A>G		intron_variant	Intron 1 of 27	1	NM_015258.2	ENSP00000238256.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16586 AN: 151960 Hom.: 1239 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.0972

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16594 AN: 152078 Hom.: 1240 Cov.: 32 AF XY: 0.112 AC XY: 8328 AN XY: 74370

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.0939

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.0404

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.135 Hom.: 2501

Bravo AF: 0.0954

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233913; hg19: chr9-115983216;