4-119320694-A-G

Variant names:

• chr4-119320694-A-G
• rs4834770
• NM_000134.4:c.216T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000134.4(FABP2):​c.216T>C​(p.Asn72Asn) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.367
• Publications: 26 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: Benign. The variant received -21 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 VariationId is 1232917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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.216T>C	p.Asn72Asn	synonymous	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.216T>C	p.Asn72Asn	synonymous	Exon 2 of 4	ENSP00000274024.3	P12104
	ENSG00000294020	ENST00000720595.1		n.176-13634A>G		intron	N/A
	ENSG00000294020	ENST00000720596.1		n.224-13634A>G		intron	N/A

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

GnomAD2 exomes AF: 0.564 AC: 130168 AN: 230746 AF XY: 0.558

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 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

African (AFR) AF: 0.553 AC: 17557 AN: 31748

American (AMR) AF: 0.636 AC: 25553 AN: 40202

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 16316 AN: 25702

East Asian (EAS) AF: 0.576 AC: 22229 AN: 38602

South Asian (SAS) AF: 0.508 AC: 41782 AN: 82244

European-Finnish (FIN) AF: 0.507 AC: 26351 AN: 51962

Middle Eastern (MID) AF: 0.547 AC: 2950 AN: 5390

European-Non Finnish (NFE) AF: 0.570 AC: 629196 AN: 1104222

Other (OTH) AF: 0.577 AC: 34289 AN: 59424

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

African (AFR) AF: 0.559 AC: 23156 AN: 41422

American (AMR) AF: 0.605 AC: 9216 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2158 AN: 3466

East Asian (EAS) AF: 0.629 AC: 3237 AN: 5148

South Asian (SAS) AF: 0.533 AC: 2571 AN: 4820

European-Finnish (FIN) AF: 0.511 AC: 5383 AN: 10532

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38503 AN: 67852

Other (OTH) AF: 0.600 AC: 1268 AN: 2112

Alfa AF: 0.570 Hom.: 73150

Bravo AF: 0.579

Asia WGS AF: 0.634 AC: 2205 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.1
DANN	Benign	0.28
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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