ENST00000508053.6:c.-566+444T>C

Variant names:

• chr5-128540043-A-G
• rs186263310
• ENST00000508053.6:c.-566+444T>C

Variant summary

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

The ENST00000508053.6(FBN2):​c.-566+444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 105,492 control chromosomes in the GnomAD database, including 548 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 0.026 (548 hom., cov: 23)
• Consequence: FBN2 ENST00000508053.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0976 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.-566+444T>C		intron_variant	Intron 5 of 14	5		ENSP00000424571.2
SLC27A6	ENST00000508645.5	c.-270+1975A>G		intron_variant	Intron 1 of 6	5		ENSP00000421759.1

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 2771 AN: 105480 Hom.: 548 Cov.: 23

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000213

Gnomad SAS AF: 0.00257

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000564

Gnomad OTH AF: 0.0205

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

GnomAD4 genome AF: 0.0263 AC: 2775 AN: 105492 Hom.: 548 Cov.: 23 AF XY: 0.0255 AC XY: 1281 AN XY: 50320

African (AFR) AF: 0.101 AC: 2621 AN: 25988

American (AMR) AF: 0.00921 AC: 85 AN: 9226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2930

East Asian (EAS) AF: 0.000214 AC: 1 AN: 4674

South Asian (SAS) AF: 0.00259 AC: 10 AN: 3866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.000564 AC: 29 AN: 51422

Other (OTH) AF: 0.0204 AC: 29 AN: 1424

Alfa AF: 0.0145 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.5
DANN	Benign	0.25
PhyloP100		0.061
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: rs186263310; hg19: chr5-127875736;