8-81480601-A-G

Variant summary

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

The NM_001442.3(FABP4):c.74-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,603,318 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (17 hom., cov: 32)
  • Exomes 𝑓: 0.015 (177 hom.)
• Consequence: FABP4 NM_001442.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003577
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0170

Genes affected

FABP4 (HGNC:3559): (fatty acid binding protein 4) FABP4 encodes the fatty acid binding protein found in adipocytes. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 8-81480601-A-G is Benign according to our data. Variant chr8-81480601-A-G is described in ClinVar as [Benign]. Clinvar id is 769744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0145 (21082/1451022) while in subpopulation NFE AF= 0.0169 (18674/1107292). AF 95% confidence interval is 0.0167. There are 177 homozygotes in gnomad4_exome. There are 10305 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FABP4	NM_001442.3	c.74-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000256104.5
LOC101927118	XR_001745980.2	n.517+18627A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FABP4	ENST00000256104.5	c.74-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001442.3	P1
	ENST00000524085.2	n.299-17316A>G		intron_variant, non_coding_transcript_variant		5
FABP4	ENST00000522659.1	c.70-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3
FABP4	ENST00000518669.5	n.143-137T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1590 AN: 152178 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0102 AC: 2468 AN: 241506 Hom.: 20 AF XY: 0.0102 AC XY: 1326 AN XY: 130596

Gnomad AFR exome AF: 0.00256

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00189

Gnomad FIN exome AF: 0.0229

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.00978

GnomAD4 exome AF: 0.0145 AC: 21082 AN: 1451022 Hom.: 177 Cov.: 31 AF XY: 0.0143 AC XY: 10305 AN XY: 721274

Gnomad4 AFR exome AF: 0.00189

Gnomad4 AMR exome AF: 0.00472

Gnomad4 ASJ exome AF: 0.00948

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00180

Gnomad4 FIN exome AF: 0.0191

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0104 AC: 1590 AN: 152296 Hom.: 17 Cov.: 32 AF XY: 0.0106 AC XY: 792 AN XY: 74480

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0129 Hom.: 8

Bravo AF: 0.00944

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.0126

EpiControl AF: 0.0148

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

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	8.9
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0
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: rs77097739; hg19: chr8-82392836;