rs145774881

Variant names:

• chr8-81283416-A-G
• rs145774881
• NM_001444.3:c.130A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-81283416-A-G
• chr8-81283416-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001444.3(FABP5):​c.130A>G​(p.Ile44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,611,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: FABP5 NM_001444.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.48
• Publications: 4 publications found

Genes affected

FABP5 (HGNC:3560): (fatty acid binding protein 5) This gene encodes the fatty acid binding protein found in epidermal cells, and was first identified as being upregulated in psoriasis tissue. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. FABPs may play roles in fatty acid uptake, transport, and metabolism. Polymorphisms in this gene are associated with type 2 diabetes. The human genome contains many pseudogenes similar to this locus.[provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016303241).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001444.3. 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
	FABP5	NM_001444.3	MANE Select	c.130A>G	p.Ile44Val	missense	Exon 2 of 4	NP_001435.1	Q01469

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FABP5	ENST00000297258.11	TSL:1 MANE Select	c.130A>G	p.Ile44Val	missense	Exon 2 of 4	ENSP00000297258.6	Q01469
	FABP5	ENST00000943582.1		c.130A>G	p.Ile44Val	missense	Exon 2 of 4	ENSP00000613641.1
	FABP5	ENST00000943583.1		c.130A>G	p.Ile44Val	missense	Exon 2 of 4	ENSP00000613642.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 249170 AF XY: 0.0000965

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00190

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.0000432 AC: 63 AN: 1459010 Hom.: 0 Cov.: 30 AF XY: 0.0000372 AC XY: 27 AN XY: 725626

African (AFR) AF: 0.0000600 AC: 2 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.00154 AC: 40 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1110922

Other (OTH) AF: 0.0000996 AC: 6 AN: 60254

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152360 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74510

African (AFR) AF: 0.000120 AC: 5 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000260 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.3
DANN	Benign	0.92
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.040
Sift	Benign	0.18	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.29
MPC		0.010
ClinPred		0.013	T
GERP RS		1.0
Varity_R		0.10
gMVP		0.27
Mutation Taster		=95/5	polymorphism

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: rs145774881; hg19: chr8-82195651; COSMIC: COSV99793062; COSMIC: COSV99793062;