rs77743612

Positions:

• chr2-24063209-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004116.5(FKBP1B):​c.*17A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,566,718 control chromosomes in the GnomAD database, including 69 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 0.0061 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (64 hom.)
• Consequence: FKBP1B NM_004116.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP1B	NM_004116.5	c.*17A>C		3_prime_UTR_variant	4/4	ENST00000380986.9	NP_004107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP1B	ENST00000380986.9	c.*17A>C		3_prime_UTR_variant	4/4	1	NM_004116.5	ENSP00000370373	P1

Frequencies

GnomAD3 genomes AF: 0.00612 AC: 931 AN: 152208 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00691

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00677 AC: 1430 AN: 211292 Hom.: 11 AF XY: 0.00684 AC XY: 771 AN XY: 112684

Gnomad AFR exome AF: 0.00102

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00132

Gnomad FIN exome AF: 0.0328

Gnomad NFE exome AF: 0.00725

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00672 AC: 9501 AN: 1414392 Hom.: 64 Cov.: 31 AF XY: 0.00650 AC XY: 4540 AN XY: 698330

Gnomad4 AFR exome AF: 0.000591

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.0000864

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.0307

Gnomad4 NFE exome AF: 0.00680

Gnomad4 OTH exome AF: 0.00595

GnomAD4 genome AF: 0.00611 AC: 930 AN: 152326 Hom.: 5 Cov.: 33 AF XY: 0.00741 AC XY: 552 AN XY: 74488

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.00692

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00621 Hom.: 0

Bravo AF: 0.00387

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.75
DANN	Benign	0.59

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: rs77743612; hg19: chr2-24286079;