rs13016301

Positions:

• chr2-24060983-A-T

Variant summary

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

The NM_004116.5(FKBP1B):​c.198+57A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,307,856 control chromosomes in the GnomAD database, including 13,000 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 0.12 (1233 hom., cov: 32)
  • Exomes 𝑓: 0.14 (11767 hom.)
• Consequence: FKBP1B NM_004116.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP1B	NM_004116.5	c.198+57A>T		intron_variant		ENST00000380986.9	NP_004107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP1B	ENST00000380986.9	c.198+57A>T		intron_variant		1	NM_004116.5	ENSP00000370373	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17684 AN: 151820 Hom.: 1232 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.136 AC: 157605 AN: 1155916 Hom.: 11767 AF XY: 0.138 AC XY: 81009 AN XY: 587922

Gnomad4 AFR exome AF: 0.0657

Gnomad4 AMR exome AF: 0.0491

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0326

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.116 AC: 17676 AN: 151940 Hom.: 1233 Cov.: 32 AF XY: 0.119 AC XY: 8858 AN XY: 74262

Gnomad4 AFR AF: 0.0685

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0420

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.106

Alfa AF: 0.130 Hom.: 173

Bravo AF: 0.102

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63

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: rs13016301; hg19: chr2-24283853;