chr5-128551760-C-T

Variant names:

• chr5-128551760-C-T
• rs6863262
• ENST00000508053.6:c.-714-8876G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000508053.6(FBN2):​c.-714-8876G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,144 control chromosomes in the GnomAD database, including 2,132 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 0.14 (2132 hom., cov: 32)
• Consequence: FBN2 ENST00000508053.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000508053.6	c.-714-8876G>A		intron_variant	Intron 3 of 14	5		ENSP00000424571.2
SLC27A6	ENST00000508645.5	c.-270+13692C>T		intron_variant	Intron 1 of 6	5		ENSP00000421759.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20916 AN: 152026 Hom.: 2116 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0783

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 20967 AN: 152144 Hom.: 2132 Cov.: 32 AF XY: 0.135 AC XY: 10032 AN XY: 74392

African (AFR) AF: 0.290 AC: 12020 AN: 41470

American (AMR) AF: 0.0782 AC: 1195 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.00561 AC: 29 AN: 5172

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4824

European-Finnish (FIN) AF: 0.0872 AC: 924 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0855 AC: 5814 AN: 67998

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.111 Hom.: 250

Bravo AF: 0.142

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6863262; hg19: chr5-127887453;