rs14388

chr2-24063319-C-T

Variant summary

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

The NM_004116.5(FKBP1B):c.*127C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 879,064 control chromosomes in the GnomAD database, including 3,883 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 (2514 hom., cov: 33)
  • Exomes 𝑓: 0.029 (1369 hom.)
• Consequence: FKBP1B NM_004116.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

Genes affected

FKBP1B (HGNC:3712): (FKBP prolyl isomerase 1B) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It is highly similar to the FK506-binding protein 1A. Its physiological role is thought to be in excitation-contraction coupling in cardiac muscle. There are two alternatively spliced transcript variants of this gene encoding different isoforms. [provided by RefSeq, Jul 2008]

MFSD2B (HGNC:37207): (MFSD2 lysolipid transporter B, sphingolipid) Enables sphingolipid transporter activity. Involved in lipid transport. Is integral component of plasma 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP1B	NM_004116.5	c.*127C>T		3_prime_UTR_variant	4/4	ENST00000380986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP1B	ENST00000380986.9	c.*127C>T		3_prime_UTR_variant	4/4	1	NM_004116.5	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17011 AN: 152176 Hom.: 2498 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0845

GnomAD4 exome AF: 0.0294 AC: 21386 AN: 726770 Hom.: 1369 Cov.: 10 AF XY: 0.0293 AC XY: 10692 AN XY: 364362

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.0466

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.0185

Gnomad4 OTH exome AF: 0.0429

GnomAD4 genome AF: 0.112 AC: 17080 AN: 152294 Hom.: 2514 Cov.: 33 AF XY: 0.109 AC XY: 8106 AN XY: 74470

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.0497

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0836

Alfa AF: 0.106 Hom.: 425

Bravo AF: 0.125

Asia WGS AF: 0.0540 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.71

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: rs14388; hg19: chr2-24286189;