Genetic Variant ENST00000356535.4:c.369A>G (chr6-122781215-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The ENST00000356535.4(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
ENST00000356535.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.504

Variant links:

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]

FABP7 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
FABP7	NM_001446.5 link	c.348+21A>G		intron_variant	Intron 3 of 3	ENST00000368444.8	NP_001437.1	O15540-1
FABP7	NM_001319039.2 link	c.369A>G	p.Pro123Pro	synonymous_variant	Exon 3 of 3		NP_001305968.1	O15540-2
FABP7	NM_001319041.2 link	c.*704A>G		3_prime_UTR_variant	Exon 2 of 2		NP_001305970.1	Q59HE4
FABP7	NM_001319042.2 link	c.336+21A>G		intron_variant	Intron 3 of 3		NP_001305971.1	A0A077H155

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FABP7	ENST00000356535.4 link	c.369A>G	p.Pro123Pro	synonymous_variant	Exon 3 of 3	1		ENSP00000348931.4		O15540-2
FABP7	ENST00000368444.8 link	c.348+21A>G		intron_variant	Intron 3 of 3	1	NM_001446.5	ENSP00000357429.3		O15540-1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

297

AN:

151960

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00359

AC XY:

485

AN XY:

135178

show subpopulations

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.:

Cov.:

AF XY:

0.00106

AC XY:

769

AN XY:

726680

show subpopulations

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.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74360

show subpopulations

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.:

Bravo

AF:

0.00214

Asia WGS

AF:

0.0120

AC:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over