chr4-119320747-T-C

Position:

• chr4-119320747-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000134.4(FABP2):​c.163A>G​(p.Thr55Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,604,502 control chromosomes in the GnomAD database, including 433,114 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41568 hom., cov: 33)
  • Exomes 𝑓: 0.73 (391546 hom.)
• Consequence: FABP2 NM_000134.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.413

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4492882E-6).
• BP6: Variant 4-119320747-T-C is Benign according to our data. Variant chr4-119320747-T-C is described in ClinVar as [Benign]. Clinvar id is 16494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP2	NM_000134.4	c.163A>G	p.Thr55Ala	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.163A>G	p.Thr55Ala	missense_variant	2/4	1	NM_000134.4	ENSP00000274024	P1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112240 AN: 151834 Hom.: 41517 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.751

GnomAD3 exomes AF: 0.726 AC: 176270 AN: 242864 Hom.: 64185 AF XY: 0.721 AC XY: 94840 AN XY: 131510

Gnomad AFR exome AF: 0.770

Gnomad AMR exome AF: 0.733

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.737

Gnomad SAS exome AF: 0.674

Gnomad FIN exome AF: 0.722

Gnomad NFE exome AF: 0.729

Gnomad OTH exome AF: 0.718

GnomAD4 exome AF: 0.734 AC: 1065485 AN: 1452550 Hom.: 391546 Cov.: 38 AF XY: 0.731 AC XY: 527879 AN XY: 722600

Gnomad4 AFR exome AF: 0.765

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.720

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.740

GnomAD4 genome AF: 0.739 AC: 112356 AN: 151952 Hom.: 41568 Cov.: 33 AF XY: 0.735 AC XY: 54544 AN XY: 74260

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.753

Alfa AF: 0.736 Hom.: 75349

Bravo AF: 0.746

TwinsUK AF: 0.725 AC: 2688

ALSPAC AF: 0.747 AC: 2878

ESP6500AA AF: 0.767 AC: 3375

ESP6500EA AF: 0.740 AC: 6360

ExAC AF: 0.726 AC: 88115

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	This variant is associated with the following publications: (PMID: 7883976, 20621703, 20047744, 19288030, 17209184, 20202768, 22838187, 19689066, 19361803, 21861348, 19384318, 14666368, 19475463, 23817228, 20329566, 21079390, 18824579, 19439328, 20484485, 11487582) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

FATTY ACID-BINDING PROTEIN, INTESTINAL, POLYMORPHISM OF Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Feb 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.39
DANN	Benign	0.78
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.24	N
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.072
Sift	Benign	0.032	D
Sift4G	Benign	0.22	T
Vest4		0.027
MPC		0.10
ClinPred		0.020	T
GERP RS		0.048
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs1799883; hg19: chr4-120241902; COSMIC: COSV56788103;