5-128538265-G-T

Position:

• chr5-128538265-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000508053.6(FBN2):​c.-439-223C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 154,854 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (176 hom., cov: 30)
  • Exomes 𝑓: 0.027 (13 hom.)
• Consequence: FBN2 ENST00000508053.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.65

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 5-128538265-G-T is Benign according to our data. Variant chr5-128538265-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 683524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4			upstream_gene_variant		ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3			upstream_gene_variant			XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9			upstream_gene_variant		1	NM_001999.4	ENSP00000262464	P1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2800 AN: 151200 Hom.: 177 Cov.: 30

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.00691

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00820

GnomAD4 exome AF: 0.0268 AC: 95 AN: 3544 Hom.: 13 Cov.: 0 AF XY: 0.0317 AC XY: 74 AN XY: 2332

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.00833

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0185 AC: 2793 AN: 151310 Hom.: 176 Cov.: 30 AF XY: 0.0207 AC XY: 1530 AN XY: 73914

Gnomad4 AFR AF: 0.00206

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.00691

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.00812

Alfa AF: 0.00750 Hom.: 3

Bravo AF: 0.0190

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 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	-0.56
CADD	Benign	18
DANN	Benign	0.95

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: rs142885655; hg19: chr5-127873958;