5-160229619-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001445.3(FABP6):c.62T>A(p.Leu21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,613,704 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L21L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.015 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (49 hom.)
• Consequence: FABP6 NM_001445.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016603768).
• BP6: Variant 5-160229619-T-A is Benign according to our data. Variant chr5-160229619-T-A is described in ClinVar as [Benign]. Clinvar id is 768048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (2289/152142) while in subpopulation AFR AF= 0.0514 (2132/41494). AF 95% confidence interval is 0.0496. There are 63 homozygotes in gnomad4. There are 1080 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FABP6	NM_001445.3	c.62T>A	p.Leu21His	missense_variant	1/4	ENST00000402432.4
FABP6	NM_001040442.1	c.209T>A	p.Leu70His	missense_variant	3/6
FABP6	NM_001130958.2	c.209T>A	p.Leu70His	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FABP6	ENST00000402432.4	c.62T>A	p.Leu21His	missense_variant	1/4	1	NM_001445.3	P1
FABP6	ENST00000393980.8	c.209T>A	p.Leu70His	missense_variant	4/7	1
FABP6	ENST00000523955.5	c.*270T>A		3_prime_UTR_variant, NMD_transcript_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2291 AN: 152024 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00741

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00383 AC: 963 AN: 251234 Hom.: 21 AF XY: 0.00264 AC XY: 359 AN XY: 135782

Gnomad AFR exome AF: 0.0507

Gnomad AMR exome AF: 0.00324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00148 AC: 2158 AN: 1461562 Hom.: 49 Cov.: 30 AF XY: 0.00125 AC XY: 908 AN XY: 727102

Gnomad4 AFR exome AF: 0.0504

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.0000666

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.0150 AC: 2289 AN: 152142 Hom.: 63 Cov.: 32 AF XY: 0.0145 AC XY: 1080 AN XY: 74394

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.00740

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00176 Hom.: 3

Bravo AF: 0.0179

ExAC AF: 0.00472 AC: 573

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	11
Dann	Benign	0.90
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.15	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.018
Sift	Benign	0.11	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0050	B;B
Vest4		0.15
MVP		0.055
MPC		0.22
ClinPred		0.00045	T
GERP RS		-3.3
Varity_R		0.11
gMVP		0.29

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: rs7720149; hg19: chr5-159656626;