4-119320694-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000134.4(FABP2):c.216T>C(p.Asn72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,591,276 control chromosomes in the GnomAD database, including 257,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24417 hom., cov: 31)
  • Exomes 𝑓: 0.57 (232767 hom.)
• Consequence: FABP2 NM_000134.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.367

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 4-119320694-A-G is Benign according to our data. Variant chr4-119320694-A-G is described in ClinVar as [Benign]. Clinvar id is 1232917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.367 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FABP2	NM_000134.4	c.216T>C	p.Asn72=	synonymous_variant	2/4	ENST00000274024.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FABP2	ENST00000274024.4	c.216T>C	p.Asn72=	synonymous_variant	2/4	1	NM_000134.4	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85970 AN: 151662 Hom.: 24384 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.597

GnomAD3 exomes AF: 0.564 AC: 130168 AN: 230746 Hom.: 37277 AF XY: 0.558 AC XY: 69968 AN XY: 125358

Gnomad AFR exome AF: 0.549

Gnomad AMR exome AF: 0.638

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.633

Gnomad SAS exome AF: 0.504

Gnomad FIN exome AF: 0.507

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.567 AC: 816223 AN: 1439496 Hom.: 232767 Cov.: 41 AF XY: 0.564 AC XY: 403847 AN XY: 716144

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.635

Gnomad4 EAS exome AF: 0.576

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.577

GnomAD4 genome AF: 0.567 AC: 86069 AN: 151780 Hom.: 24417 Cov.: 31 AF XY: 0.564 AC XY: 41820 AN XY: 74150

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.600

Alfa AF: 0.570 Hom.: 45312

Bravo AF: 0.579

Asia WGS AF: 0.634 AC: 2205 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	3.1
Dann	Benign	0.28

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: rs4834770; hg19: chr4-120241849; COSMIC: COSV56788801;