Genetic Variant FKBP1B:c.*17A>C (chr2-24063209-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

2 publications found

Variant links:

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]

FKBP1B links:

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]

MFSD2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BS2

High AC in GnomAd4 at 930 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004116.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FKBP1B	NM_004116.5	MANE Select	c.*17A>C	3_prime_UTR	Exon 4 of 4	NP_004107.1	P68106-1
FKBP1B	NM_054033.4		c.*146A>C	3_prime_UTR	Exon 4 of 4	NP_473374.1	P68106-2
FKBP1B	NM_001322963.2		c.*17A>C	3_prime_UTR	Exon 5 of 5	NP_001309892.1	F8W6G9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FKBP1B	ENST00000380986.9	TSL:1 MANE Select	c.*17A>C	3_prime_UTR	Exon 4 of 4	ENSP00000370373.4	P68106-1
FKBP1B	ENST00000380991.8	TSL:1	c.*146A>C	3_prime_UTR	Exon 4 of 4	ENSP00000370379.4	P68106-2
FKBP1B	ENST00000438630.5	TSL:1	n.*372A>C	non_coding_transcript_exon	Exon 6 of 6	ENSP00000416349.1	G5E9U6

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

931

AN:

152208

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00677

AC:

1430

AN:

211292

AF XY:

0.00684

show subpopulations

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 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.:

Cov.:

AF XY:

0.00650

AC XY:

4540

AN XY:

698330

show subpopulations

African (AFR)

AF:

0.000591

AC:

AN:

32142

American (AMR)

AF:

0.00206

AC:

AN:

38350

Ashkenazi Jewish (ASJ)

AF:

0.0000864

AC:

AN:

23150

East Asian (EAS)

AF:

0.00

AC:

AN:

39164

South Asian (SAS)

AF:

0.00119

AC:

AN:

77962

European-Finnish (FIN)

AF:

0.0307

AC:

1554

AN:

50690

Middle Eastern (MID)

AF:

0.000362

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.00680

AC:

7405

AN:

1089124

Other (OTH)

AF:

0.00595

AC:

347

AN:

58292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

481

963

1444

1926

2407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00611

AC:

930

AN:

152326

Hom.:

Cov.:

AF XY:

0.00741

AC XY:

552

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41582

American (AMR)

AF:

0.00261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0345

AC:

366

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00692

AC:

471

AN:

68016

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

151

202

252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00621

Hom.:

Bravo

AF:

0.00387

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.75

(source)

DANN

Benign

0.59

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over