2-24060983-A-T

Variant names:

• chr2-24060983-A-T
• rs13016301
• NM_004116.5:c.198+57A>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1B	NM_004116.5	MANE Select	c.198+57A>T		intron	N/A	NP_004107.1
	FKBP1B	NM_054033.4		c.198+57A>T		intron	N/A	NP_473374.1
	FKBP1B	NM_001322963.2		c.111+57A>T		intron	N/A	NP_001309892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1B	ENST00000380986.9	TSL:1 MANE Select	c.198+57A>T		intron	N/A	ENSP00000370373.4
	FKBP1B	ENST00000380991.8	TSL:1	c.198+57A>T		intron	N/A	ENSP00000370379.4
	FKBP1B	ENST00000438630.5	TSL:1	n.*181+57A>T		intron	N/A	ENSP00000416349.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17684 AN: 151820 Hom.: 1232 Cov.: 32

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

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

GnomAD4 genome AF: 0.116 AC: 17676 AN: 151940 Hom.: 1233 Cov.: 32 AF XY: 0.119 AC XY: 8858 AN XY: 74262

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: 24 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9547 AN: 67946

Other (OTH) AF: 0.106 AC: 223 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-1.3
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: rs13016301; hg19: chr2-24283853;