rs1130435

Positions:

• chr5-160232266-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001445.3(FABP6):​c.236C>T​(p.Thr79Met) variant causes a missense change. The variant allele was found at a frequency of 0.419 in 1,602,626 control chromosomes in the GnomAD database, including 142,246 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 0.43 (14546 hom., cov: 30)
  • Exomes 𝑓: 0.42 (127700 hom.)
• Consequence: FABP6 NM_001445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42

Genes affected

FABP6 (HGNC:3561): (fatty acid binding protein 6) This gene encodes the ileal fatty acid binding protein. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. FABP6 and FABP1 (the liver fatty acid binding protein) are also able to bind bile acids. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. Transcript variants generated by alternate transcription promoters and/or alternate splicing have been found for this gene. [provided by RefSeq, Jul 2008]

FABP6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3707747E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP6	NM_001445.3	c.236C>T	p.Thr79Met	missense_variant	2/4	ENST00000402432.4	NP_001436.1
FABP6	NM_001040442.1	c.383C>T	p.Thr128Met	missense_variant	4/6		NP_001035532.1
FABP6	NM_001130958.2	c.383C>T	p.Thr128Met	missense_variant	5/7		NP_001124430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP6	ENST00000402432.4	c.236C>T	p.Thr79Met	missense_variant	2/4	1	NM_001445.3	ENSP00000385433.4

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65898 AN: 151594 Hom.: 14532 Cov.: 30

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.415

GnomAD3 exomes AF: 0.443 AC: 104038 AN: 235094 Hom.: 23170 AF XY: 0.444 AC XY: 56241 AN XY: 126770

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.473

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.508

Gnomad SAS exome AF: 0.532

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.435

GnomAD4 exome AF: 0.417 AC: 605556 AN: 1450912 Hom.: 127700 Cov.: 36 AF XY: 0.420 AC XY: 303116 AN XY: 720912

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.530

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.435 AC: 65954 AN: 151714 Hom.: 14546 Cov.: 30 AF XY: 0.439 AC XY: 32560 AN XY: 74100

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.414

Alfa AF: 0.411 Hom.: 22450

Bravo AF: 0.432

TwinsUK AF: 0.403 AC: 1496

ALSPAC AF: 0.398 AC: 1535

ESP6500AA AF: 0.463 AC: 2042

ESP6500EA AF: 0.400 AC: 3443

ExAC AF: 0.431 AC: 52291

Asia WGS AF: 0.524 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.047	.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.92	D;D
MetaRNN	Benign	0.00024	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.080	N;N
REVEL	Benign	0.074
Sift	Benign	0.10	T;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.26	B;B
Vest4		0.089
MPC		0.20
ClinPred		0.028	T
GERP RS		3.5
Varity_R		0.28
gMVP		0.49

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: rs1130435; hg19: chr5-159659273; COSMIC: COSV67437401;