rs17848133

Positions:

• chr6-122781215-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_001319039.2(FABP7):​c.369A>G​(p.Pro123Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,612,892 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0020 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (28 hom.)
• Consequence: FABP7 NM_001319039.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

Genes affected

FABP7 (HGNC:3562): (fatty acid binding protein 7) The gene encodes a small, highly conserved cytoplasmic protein that bind long-chain fatty acids and other hydrophobic ligands. The encoded protein is important in the establishment of the radial glial fiber in the developing brain. Alternative splicing and promoter usage results in multiple transcript variants encoding different isoforms. Pseudogenes of this gene are found on multiple chromosomes. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.504 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00196 (298/152076) while in subpopulation EAS AF= 0.0506 (262/5178). AF 95% confidence interval is 0.0456. There are 6 homozygotes in gnomad4. There are 169 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FABP7	NM_001446.5	c.348+21A>G		intron_variant		ENST00000368444.8	NP_001437.1
FABP7	NM_001319039.2	c.369A>G	p.Pro123Pro	synonymous_variant	3/3		NP_001305968.1
FABP7	NM_001319041.2	c.*704A>G		3_prime_UTR_variant	2/2		NP_001305970.1
FABP7	NM_001319042.2	c.336+21A>G		intron_variant			NP_001305971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FABP7	ENST00000356535.4	c.369A>G	p.Pro123Pro	synonymous_variant	3/3	1		ENSP00000348931.4
FABP7	ENST00000368444.8	c.348+21A>G		intron_variant		1	NM_001446.5	ENSP00000357429.3

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 297 AN: 151960 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00394 AC: 985 AN: 250154 Hom.: 27 AF XY: 0.00359 AC XY: 485 AN XY: 135178

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0500

Gnomad SAS exome AF: 0.00138

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00108 AC: 1579 AN: 1460816 Hom.: 28 Cov.: 30 AF XY: 0.00106 AC XY: 769 AN XY: 726680

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0308

Gnomad4 SAS exome AF: 0.00145

Gnomad4 FIN exome AF: 0.000637

Gnomad4 NFE exome AF: 0.0000639

Gnomad4 OTH exome AF: 0.00201

GnomAD4 genome AF: 0.00196 AC: 298 AN: 152076 Hom.: 6 Cov.: 32 AF XY: 0.00227 AC XY: 169 AN XY: 74360

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000538 Hom.: 0

Bravo AF: 0.00214

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.53
DANN	Benign	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: rs17848133; hg19: chr6-123102360; COSMIC: COSV62956605;