5-160229620-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001445.3(FABP6):c.63C>T(p.Leu21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,613,682 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (49 hom.)
• Consequence: FABP6 NM_001445.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.940

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-160229620-C-T is Benign according to our data. Variant chr5-160229620-C-T is described in ClinVar as [Benign]. Clinvar id is 768049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.94 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (2287/152146) while in subpopulation AFR AF= 0.0513 (2130/41494). AF 95% confidence interval is 0.0495. There are 63 homozygotes in gnomad4. There are 1079 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.63C>T	p.Leu21=	synonymous_variant	1/4	ENST00000402432.4
FABP6	NM_001040442.1	c.210C>T	p.Leu70=	synonymous_variant	3/6
FABP6	NM_001130958.2	c.210C>T	p.Leu70=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FABP6	ENST00000402432.4	c.63C>T	p.Leu21=	synonymous_variant	1/4	1	NM_001445.3	P1
FABP6	ENST00000393980.8	c.210C>T	p.Leu70=	synonymous_variant	4/7	1
FABP6	ENST00000523955.5	c.*271C>T		3_prime_UTR_variant, NMD_transcript_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2289 AN: 152028 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00740

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: 251210 Hom.: 21 AF XY: 0.00264 AC XY: 359 AN XY: 135780

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: 2157 AN: 1461536 Hom.: 49 Cov.: 30 AF XY: 0.00125 AC XY: 907 AN XY: 727080

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: 0.000116

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.0000666

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.0150 AC: 2287 AN: 152146 Hom.: 63 Cov.: 32 AF XY: 0.0145 AC XY: 1079 AN XY: 74396

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.00740

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00621 Hom.: 17

Bravo AF: 0.0179

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.7
Dann	Benign	0.56

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: rs7734547; hg19: chr5-159656627;