ENST00000438630.5:n.*482C>T

Variant names:

• chr2-24063319-C-T
• rs14388
• ENST00000438630.5:n.*482C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000438630.5(FKBP1B):​n.*482C>T variant causes a non coding transcript exon 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 ENST00000438630.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000438630.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1B	NM_004116.5	MANE Select	c.*127C>T		3_prime_UTR	Exon 4 of 4	NP_004107.1
	FKBP1B	NR_136536.2		n.765C>T		non_coding_transcript_exon	Exon 6 of 6
	FKBP1B	NR_136538.2		n.697C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1B	ENST00000438630.5	TSL:1	n.*482C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000416349.1
	FKBP1B	ENST00000380986.9	TSL:1 MANE Select	c.*127C>T		3_prime_UTR	Exon 4 of 4	ENSP00000370373.4
	FKBP1B	ENST00000380991.8	TSL:1	c.*256C>T		3_prime_UTR	Exon 4 of 4	ENSP00000370379.4

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

African (AFR) AF: 0.352 AC: 5787 AN: 16428

American (AMR) AF: 0.0385 AC: 533 AN: 13828

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 218 AN: 14840

East Asian (EAS) AF: 0.0204 AC: 586 AN: 28792

South Asian (SAS) AF: 0.0466 AC: 2064 AN: 44308

European-Finnish (FIN) AF: 0.0193 AC: 597 AN: 30948

Middle Eastern (MID) AF: 0.0513 AC: 135 AN: 2632

European-Non Finnish (NFE) AF: 0.0185 AC: 9971 AN: 540178

Other (OTH) AF: 0.0429 AC: 1495 AN: 34816

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

African (AFR) AF: 0.343 AC: 14236 AN: 41528

American (AMR) AF: 0.0497 AC: 760 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5186

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4832

European-Finnish (FIN) AF: 0.0182 AC: 193 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1380 AN: 68032

Other (OTH) AF: 0.0836 AC: 177 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.71
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs14388; hg19: chr2-24286189;