4-119320747-T-G

Variant names:

• chr4-119320747-T-G
• rs1799883
• NM_000134.4:c.163A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000134.4(FABP2):​c.163A>C​(p.Thr55Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T55A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FABP2 NM_000134.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 287 publications found

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]

ENSG00000294020 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25817645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000134.4. 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
	FABP2	NM_000134.4	MANE Select	c.163A>C	p.Thr55Pro	missense	Exon 2 of 4	NP_000125.2	P12104

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FABP2	ENST00000274024.4	TSL:1 MANE Select	c.163A>C	p.Thr55Pro	missense	Exon 2 of 4	ENSP00000274024.3	P12104
	ENSG00000294020	ENST00000720595.1		n.176-13581T>G		intron	N/A
	ENSG00000294020	ENST00000720596.1		n.224-13581T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454356 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 723480

African (AFR) AF: 0.00 AC: 0 AN: 32898

American (AMR) AF: 0.00 AC: 0 AN: 43198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39270

South Asian (SAS) AF: 0.00 AC: 0 AN: 84786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109310

Other (OTH) AF: 0.00 AC: 0 AN: 60064

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.6
DANN	Benign	0.84
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.40	N
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.41
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.060
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.17	T
Vest4		0.31
MutPred		0.68		Loss of stability (P = 0.0484)
MVP		0.072
MPC		0.14
ClinPred		0.51	D
GERP RS		0.048
gMVP		0.76
Mutation Taster		=97/3	polymorphism

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: rs1799883; hg19: chr4-120241902;