Genetic Variant NM_004116.5:c.198+57A>T (chr2-24060983-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

3 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 -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 rank	MANE	Protein	UniProt
FKBP1B	NM_004116.5 link	c.198+57A>T		intron_variant	Intron 3 of 3	ENST00000380986.9	NP_004107.1	P68106-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKBP1B	ENST00000380986.9 link	c.198+57A>T		intron_variant	Intron 3 of 3	1	NM_004116.5	ENSP00000370373.4		P68106-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17684

AN:

151820

Hom.:

1232

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0657

AC:

1778

AN:

27052

American (AMR)

AF:

0.0491

AC:

2079

AN:

42362

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

2799

AN:

23500

East Asian (EAS)

AF:

0.0326

AC:

1205

AN:

36992

South Asian (SAS)

AF:

0.173

AC:

13376

AN:

77416

European-Finnish (FIN)

AF:

0.205

AC:

10767

AN:

52406

Middle Eastern (MID)

AF:

0.0872

AC:

455

AN:

5216

European-Non Finnish (NFE)

AF:

0.141

AC:

118787

AN:

841024

Other (OTH)

AF:

0.127

AC:

6359

AN:

49948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6574

13148

19723

26297

32871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.116

AC:

17676

AN:

151940

Hom.:

1233

Cov.:

AF XY:

0.119

AC XY:

8858

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0685

AC:

2837

AN:

41432

American (AMR)

AF:

0.0734

AC:

1121

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

386

AN:

3462

East Asian (EAS)

AF:

0.0420

AC:

217

AN:

5170

South Asian (SAS)

AF:

0.180

AC:

862

AN:

4798

European-Finnish (FIN)

AF:

0.225

AC:

2375

AN:

10542

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9547

AN:

67946

Other (OTH)

AF:

0.106

AC:

223

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

774

1548

2323

3097

3871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.63

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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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NM_004116.5:c.198+57A>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over