5-128538300-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000508053.6(FBN2):c.-439-258C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 154,768 control chromosomes in the GnomAD database, including 1,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1168 hom., cov: 29)
  • Exomes 𝑓: 0.064 (8 hom.)
• Consequence: FBN2 ENST00000508053.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.552

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

SLC27A6 (HGNC:11000): (solute carrier family 27 member 6) This gene encodes a member of the fatty acid transport protein family (FATP). FATPs are involved in the uptake of long-chain fatty acids and have unique expression patterns. Alternatively spliced transcript variants encoding the same protein 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 (BayesDel_noAF=-0.49).
• BP6: Variant 5-128538300-G-C is Benign according to our data. Variant chr5-128538300-G-C is described in ClinVar as [Benign]. Clinvar id is 683521.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000508053.6	c.-439-258C>G		intron_variant		5
SLC27A6	ENST00000508645.5	c.-270+232G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18184 AN: 151088 Hom.: 1164 Cov.: 29

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0640 AC: 229 AN: 3576 Hom.: 8 AF XY: 0.0598 AC XY: 140 AN XY: 2342

Gnomad4 AFR exome AF: 0.0909

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.0800

Gnomad4 FIN exome AF: 0.0238

Gnomad4 NFE exome AF: 0.0627

Gnomad4 OTH exome AF: 0.0616

GnomAD4 genome AF: 0.120 AC: 18186 AN: 151192 Hom.: 1168 Cov.: 29 AF XY: 0.119 AC XY: 8783 AN XY: 73830

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.0659

Gnomad4 SAS AF: 0.0906

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.102

Alfa AF: 0.116 Hom.: 143

Bravo AF: 0.122

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

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	17
Dann	Benign	0.85

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: rs141359565; hg19: chr5-127873993;