4-119320776-C-A

Variant names:

• chr4-119320776-C-A
• rs752892343
• NM_000134.4:c.134G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000134.4(FABP2):​c.134G>T​(p.Gly45Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G45E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FABP2 NM_000134.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.59
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.933

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.134G>T	p.Gly45Val	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.134G>T	p.Gly45Val	missense	Exon 2 of 4	ENSP00000274024.3	P12104
	ENSG00000294020	ENST00000720595.1		n.176-13552C>A		intron	N/A
	ENSG00000294020	ENST00000720596.1		n.224-13552C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000412 AC: 1 AN: 242918 AF XY: 0.00000760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453850 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723212

African (AFR) AF: 0.00 AC: 0 AN: 32846

American (AMR) AF: 0.00 AC: 0 AN: 42966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39176

South Asian (SAS) AF: 0.00 AC: 0 AN: 84588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109302

Other (OTH) AF: 0.00 AC: 0 AN: 60072

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-1.0	T
PhyloP100		4.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Vest4		0.84
MutPred		0.79		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.37
MPC		0.59
ClinPred		1.0	D
GERP RS		5.3
gMVP		0.89
Mutation Taster		=36/64	disease causing

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: rs752892343; hg19: chr4-120241931;