rs1424344

Variant names:

• chr2-24061096-C-T
• rs1424344
• NM_004116.5:c.198+170C>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+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
• Publications: 2 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1B	NM_004116.5	MANE Select	c.198+170C>T		intron	N/A	NP_004107.1
	FKBP1B	NM_054033.4		c.198+170C>T		intron	N/A	NP_473374.1
	FKBP1B	NM_001322963.2		c.111+170C>T		intron	N/A	NP_001309892.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP1B	ENST00000380986.9	TSL:1 MANE Select	c.198+170C>T		intron	N/A	ENSP00000370373.4
	FKBP1B	ENST00000380991.8	TSL:1	c.198+170C>T		intron	N/A	ENSP00000370379.4
	FKBP1B	ENST00000438630.5	TSL:1	n.*181+170C>T		intron	N/A	ENSP00000416349.1

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

African (AFR) AF: 0.343 AC: 14191 AN: 41424

American (AMR) AF: 0.112 AC: 1710 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5178

South Asian (SAS) AF: 0.0768 AC: 371 AN: 4832

European-Finnish (FIN) AF: 0.0901 AC: 954 AN: 10586

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8256 AN: 67976

Other (OTH) AF: 0.154 AC: 326 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		0.80
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: rs1424344; hg19: chr2-24283966;