rs1424344

chr2-24061096-C-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+170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,076 control chromosomes in the GnomAD database, including 3,213 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 0.17 (3213 hom., cov: 32)
• Consequence: FKBP1B NM_004116.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKBP1B	NM_004116.5	c.198+170C>T		intron_variant		ENST00000380986.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKBP1B	ENST00000380986.9	c.198+170C>T		intron_variant		1	NM_004116.5	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26348 AN: 151958 Hom.: 3201 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.174 AC: 26400 AN: 152076 Hom.: 3213 Cov.: 32 AF XY: 0.167 AC XY: 12454 AN XY: 74376

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.00772

Gnomad4 SAS AF: 0.0768

Gnomad4 FIN AF: 0.0901

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.154

Alfa AF: 0.158 Hom.: 420

Bravo AF: 0.183

Asia WGS AF: 0.0710 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.94

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: rs1424344; hg19: chr2-24283966;