4-119319083-T-G

Variant names:

• chr4-119319083-T-G
• rs1511025
• NM_000134.4:c.357A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000134.4(FABP2):​c.357A>C​(p.Val119Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V119V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FABP2 NM_000134.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP2	NM_000134.4	c.357A>C	p.Val119Val	synonymous_variant	Exon 4 of 4	ENST00000274024.4	NP_000125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP2	ENST00000274024.4	c.357A>C	p.Val119Val	synonymous_variant	Exon 4 of 4	1	NM_000134.4	ENSP00000274024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443808 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 718738

African (AFR) AF: 0.00 AC: 0 AN: 32420

American (AMR) AF: 0.00 AC: 0 AN: 41354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 38688

South Asian (SAS) AF: 0.00 AC: 0 AN: 83864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1103102

Other (OTH) AF: 0.00 AC: 0 AN: 59578

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.41
PhyloP100		-2.1

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: rs1511025; hg19: chr4-120240238;