2-24055971-T-G

Position:

• chr2-24055971-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004116.5(FKBP1B):​c.85+2022T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,968 control chromosomes in the GnomAD database, including 7,136 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 0.29 (7136 hom., cov: 32)
• Consequence: FKBP1B NM_004116.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

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]

FKBP1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKBP1B	NM_004116.5	c.85+2022T>G		intron_variant		ENST00000380986.9	NP_004107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKBP1B	ENST00000380986.9	c.85+2022T>G		intron_variant		1	NM_004116.5	ENSP00000370373.4

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44494 AN: 151850 Hom.: 7122 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.293 AC: 44537 AN: 151968 Hom.: 7136 Cov.: 32 AF XY: 0.290 AC XY: 21536 AN XY: 74290

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0498

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.262

Alfa AF: 0.262 Hom.: 7211

Bravo AF: 0.289

Asia WGS AF: 0.172 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.40

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: rs7568163; hg19: chr2-24278841;