Variant chr5-128538114-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001999.4(FBN2):c.-511G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 157,096 control chromosomes in the GnomAD database, including 18,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.44 ( 18624 hom., cov: 32)

Exomes 𝑓: 0.34 ( 323 hom. )

Consequence

FBN2
NM_001999.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.305

Variant links:

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]

FBN2 links:

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]

SLC27A6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 5-128538114-C-T is Benign according to our data. Variant chr5-128538114-C-T is described in ClinVar as [Benign]. Clinvar id is 675097.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.-511G>A		5_prime_UTR_variant	1/65	ENST00000262464.9
FBN2	XM_017009228.3 linkuse as main transcript	c.-511G>A		5_prime_UTR_variant	1/64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.-511G>A		5_prime_UTR_variant	1/65	1	NM_001999.4	P1	P35556-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66574

AN:

151834

Hom.:

18584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.804

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.335

AC:

1727

AN:

5152

Hom.:

323

Cov.:

AF XY:

0.329

AC XY:

921

AN XY:

2796

show subpopulations

Gnomad4 AFR exome

AF:

0.714

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.343

Gnomad4 FIN exome

AF:

0.364

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.439

AC:

66671

AN:

151944

Hom.:

18624

Cov.:

AF XY:

0.431

AC XY:

32021

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.804

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.383

Hom.:

1745

Bravo

AF:

0.453

Asia WGS

AF:

0.351

AC:

1219

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.86

CADD

Benign

7.0

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over