rs2241883

Variant names:

• chr2-88124547-T-C
• rs2241883
• NM_001443.3:c.280A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001443.3(FABP1):​c.280A>G​(p.Thr94Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,609,742 control chromosomes in the GnomAD database, including 78,312 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6995 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71317 hom.)
• Consequence: FABP1 NM_001443.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553
• Publications: 106 publications found

Genes affected

FABP1 (HGNC:3555): (fatty acid binding protein 1) This gene encodes the fatty acid binding protein found in liver. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. This protein and FABP6 (the ileal fatty acid binding protein) are also able to bind bile acids. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013678968).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FABP1	NM_001443.3	c.280A>G	p.Thr94Ala	missense_variant	Exon 3 of 4	ENST00000295834.8	NP_001434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP1	ENST00000295834.8	c.280A>G	p.Thr94Ala	missense_variant	Exon 3 of 4	1	NM_001443.3	ENSP00000295834.3
FABP1	ENST00000393750.3	c.280A>G	p.Thr94Ala	missense_variant	Exon 3 of 3	2		ENSP00000377351.3
FABP1	ENST00000495375.1	n.566A>G		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43552 AN: 151928 Hom.: 6991 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.303 AC: 75214 AN: 248312 AF XY: 0.299

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.335

Gnomad EAS exome AF: 0.204

Gnomad FIN exome AF: 0.492

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.307 AC: 446857 AN: 1457694 Hom.: 71317 Cov.: 33 AF XY: 0.304 AC XY: 220408 AN XY: 725192

African (AFR) AF: 0.165 AC: 5503 AN: 33364

American (AMR) AF: 0.308 AC: 13610 AN: 44182

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8884 AN: 26094

East Asian (EAS) AF: 0.222 AC: 8781 AN: 39538

South Asian (SAS) AF: 0.174 AC: 14909 AN: 85596

European-Finnish (FIN) AF: 0.481 AC: 25678 AN: 53368

Middle Eastern (MID) AF: 0.231 AC: 1331 AN: 5760

European-Non Finnish (NFE) AF: 0.316 AC: 350198 AN: 1109596

Other (OTH) AF: 0.298 AC: 17963 AN: 60196

GnomAD4 genome AF: 0.287 AC: 43584 AN: 152048 Hom.: 6995 Cov.: 32 AF XY: 0.290 AC XY: 21575 AN XY: 74302

African (AFR) AF: 0.172 AC: 7150 AN: 41506

American (AMR) AF: 0.298 AC: 4547 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1177 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1113 AN: 5164

South Asian (SAS) AF: 0.158 AC: 761 AN: 4824

European-Finnish (FIN) AF: 0.503 AC: 5307 AN: 10548

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22485 AN: 67960

Other (OTH) AF: 0.287 AC: 605 AN: 2108

Alfa AF: 0.309 Hom.: 35150

Bravo AF: 0.272

TwinsUK AF: 0.312 AC: 1157

ALSPAC AF: 0.314 AC: 1211

ESP6500AA AF: 0.167 AC: 736

ESP6500EA AF: 0.323 AC: 2774

ExAC AF: 0.298 AC: 36216

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.36	T;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		0.55
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.066
Sift	Benign	0.56	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.0	B;B
Vest4		0.098
MPC		0.25
ClinPred		0.0055	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.48
Mutation Taster		=98/2	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: rs2241883; hg19: chr2-88424066; COSMIC: COSV55559009; COSMIC: COSV55559009;