Variant 5-128258040-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.*1415G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,806 control chromosomes in the GnomAD database, including 7,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 7980 hom., cov: 32)

Exomes 𝑓: 0.16 ( 4 hom. )

Consequence

FBN2
NM_001999.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.390

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:

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=-0.92).

BP6

Variant 5-128258040-C-T is Benign according to our data. Variant chr5-128258040-C-T is described in ClinVar as [Benign]. Clinvar id is 350729.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN2	NM_001999.4 linkuse as main transcript	c.*1415G>A		3_prime_UTR_variant	65/65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3 linkuse as main transcript	c.*1415G>A		3_prime_UTR_variant	64/64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9 linkuse as main transcript	c.*1415G>A		3_prime_UTR_variant	65/65	1	NM_001999.4	ENSP00000262464	P1	P35556-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37556

AN:

151268

Hom.:

7949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.0401

Gnomad SAS

AF:

0.0720

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.164

AC:

AN:

432

Hom.:

Cov.:

AF XY:

0.185

AC XY:

AN XY:

260

show subpopulations

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.249

AC:

37636

AN:

151374

Hom.:

7980

Cov.:

AF XY:

0.244

AC XY:

18049

AN XY:

73952

show subpopulations

Gnomad4 AFR

AF:

0.586

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.0755

Gnomad4 EAS

AF:

0.0404

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.195

Alfa

AF:

0.113

Hom.:

624

Bravo

AF:

0.264

Asia WGS

AF:

0.0910

AC:

317

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital contractural arachnodactyly

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.21

DANN

Benign

0.34

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