chr2-88124547-T-C

Position:

• chr2-88124547-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

FABP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FABP1	NM_001443.3	c.280A>G	p.Thr94Ala	missense_variant	3/4	ENST00000295834.8	NP_001434.1

Ensembl

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

GnomAD3 exomes AF: 0.303 AC: 75214 AN: 248312 Hom.: 12506 AF XY: 0.299 AC XY: 40183 AN XY: 134296

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 SAS exome AF: 0.174

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

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.298

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

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.287

Alfa AF: 0.314 Hom.: 19433

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;.
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

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: rs2241883; hg19: chr2-88424066; COSMIC: COSV55559009; COSMIC: COSV55559009;