5-128538274-A-G

Position:

• chr5-128538274-A-G

Variant summary

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

The ENST00000508053.6(FBN2):​c.-439-232T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,572 control chromosomes in the GnomAD database, including 1,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1173 hom., cov: 29)
  • Exomes 𝑓: 0.069 (8 hom.)
• Consequence: FBN2 ENST00000508053.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.499

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=-0.51).
• BP6: Variant 5-128538274-A-G is Benign according to our data. Variant chr5-128538274-A-G is described in ClinVar as [Benign]. Clinvar id is 683523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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	ENST00000508053.6	c.-439-232T>C		intron_variant		5		ENSP00000424571
SLC27A6	ENST00000508645.5	c.-270+206A>G		intron_variant		5		ENSP00000421759
FBN2	ENST00000262464.9			upstream_gene_variant		1	NM_001999.4	ENSP00000262464	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18212 AN: 149210 Hom.: 1169 Cov.: 29

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0680

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0689 AC: 224 AN: 3252 Hom.: 8 AF XY: 0.0633 AC XY: 136 AN XY: 2150

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0667

Gnomad4 ASJ exome AF: 0.0500

Gnomad4 EAS exome AF: 0.00847

Gnomad4 SAS exome AF: 0.0822

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0654

Gnomad4 OTH exome AF: 0.0956

GnomAD4 genome AF: 0.122 AC: 18214 AN: 149320 Hom.: 1173 Cov.: 29 AF XY: 0.121 AC XY: 8810 AN XY: 72900

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0878

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.0680

Gnomad4 SAS AF: 0.0926

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.105

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	-0.51
CADD	Benign	19
DANN	Benign	0.67

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: rs138741640; hg19: chr5-127873967;