4-119320776-C-T

Position:

• chr4-119320776-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000134.4(FABP2):​c.134G>A​(p.Gly45Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FABP2 NM_000134.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59

Genes affected

FABP2 (HGNC:3556): (fatty acid binding protein 2) The protein encoded by this gene is an intracellular fatty acid-binding protein that participates in the uptake, intracellular metabolism, and transport of long-chain fatty acids. The encoded protein is also involved in the modulation of cell growth and proliferation. This protein binds saturated long-chain fatty acids with high affinity, and may act as a lipid sensor to maintain energy homeostasis. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP2	NM_000134.4	c.134G>A	p.Gly45Glu	missense_variant	2/4	ENST00000274024.4	NP_000125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP2	ENST00000274024.4	c.134G>A	p.Gly45Glu	missense_variant	2/4	1	NM_000134.4	ENSP00000274024.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.134G>A (p.G45E) alteration is located in exon 2 (coding exon 2) of the FABP2 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the glycine (G) at amino acid position 45 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.25
Sift	Benign	0.033	D
Sift4G	Benign	0.099	T
Vest4		0.46
MutPred		0.83		Gain of solvent accessibility (P = 0.024);
MVP		0.27
MPC		0.50
ClinPred		0.99	D
GERP RS		5.3
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-120241931;