5-128538228-C-G

Position:

• chr5-128538228-C-G

Variant summary

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

The ENST00000262464.9(FBN2):​c.-625G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 153,932 control chromosomes in the GnomAD database, including 615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (609 hom., cov: 30)
  • Exomes 𝑓: 0.059 (6 hom.)
• Consequence: FBN2 ENST00000262464.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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=-0.76).
• BP6: Variant 5-128538228-C-G is Benign according to our data. Variant chr5-128538228-C-G is described in ClinVar as [Benign]. Clinvar id is 683525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4	c.-625G>C		5_prime_UTR_variant	1/65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.-625G>C		5_prime_UTR_variant	1/64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.-625G>C		5_prime_UTR_variant	1/65	1	NM_001999.4	ENSP00000262464	P1

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12110 AN: 150868 Hom.: 610 Cov.: 30

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.0665

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0768

GnomAD4 exome AF: 0.0586 AC: 173 AN: 2954 Hom.: 6 Cov.: 0 AF XY: 0.0577 AC XY: 104 AN XY: 1802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.0145

Gnomad4 SAS exome AF: 0.0703

Gnomad4 FIN exome AF: 0.0342

Gnomad4 NFE exome AF: 0.0606

Gnomad4 OTH exome AF: 0.0726

GnomAD4 genome AF: 0.0802 AC: 12105 AN: 150978 Hom.: 609 Cov.: 30 AF XY: 0.0796 AC XY: 5870 AN XY: 73702

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.0884

Gnomad4 EAS AF: 0.0661

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0760

Alfa AF: 0.0919 Hom.: 106

Bravo AF: 0.0754

Asia WGS AF: 0.0870 AC: 302 AN: 3470

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	-0.76
CADD	Benign	16
DANN	Benign	0.57

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: rs147684576; hg19: chr5-127873921;