rs169494

Positions:

• chr6-32130099-G-A

Variant summary

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

The NM_022110.4(FKBPL):​c.-79C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 500,408 control chromosomes in the GnomAD database, including 4,705 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 0.10 (1009 hom., cov: 31)
  • Exomes 𝑓: 0.11 (3696 hom.)
• Consequence: FKBPL NM_022110.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

Genes affected

FKBPL (HGNC:13949): (FKBP prolyl isomerase like) The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBPL	NM_022110.4	c.-79C>T		5_prime_UTR_variant	1/2	ENST00000375156.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBPL	ENST00000375156.4	c.-79C>T		5_prime_UTR_variant	1/2	1	NM_022110.4	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15491 AN: 152014 Hom.: 1004 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.113 AC: 39492 AN: 348276 Hom.: 3696 Cov.: 0 AF XY: 0.128 AC XY: 23817 AN XY: 185592

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0883

Gnomad4 ASJ exome AF: 0.0688

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.0691

Gnomad4 NFE exome AF: 0.0785

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.102 AC: 15515 AN: 152132 Hom.: 1009 Cov.: 31 AF XY: 0.107 AC XY: 7936 AN XY: 74348

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0771

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0824 Hom.: 862

Bravo AF: 0.101

Asia WGS AF: 0.228 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
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: rs169494; hg19: chr6-32097876;