Variant chr22-45518812-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006486.3(FBLN1):c.185+25T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 1,548,336 control chromosomes in the GnomAD database, including 4,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 369 hom., cov: 32)

Exomes 𝑓: 0.072 ( 3935 hom. )

Consequence

FBLN1
NM_006486.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.649

Variant links:

Genes affected

FBLN1 (HGNC:3600): (fibulin 1) Fibulin 1 is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix. Calcium-binding is apparently required to mediate its binding to laminin and nidogen. It mediates platelet adhesion via binding fibrinogen. Four splice variants which differ in the 3' end have been identified. Each variant encodes a different isoform, but no functional distinctions have been identified among the four variants. [provided by RefSeq, Jul 2008]

FBLN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-45518812-T-G is Benign according to our data. Variant chr22-45518812-T-G is described in ClinVar as [Benign]. Clinvar id is 1279638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FBLN1	NM_006486.3 linkuse as main transcript	c.185+25T>G	intron_variant	ENST00000327858.11
FBLN1	NM_001996.4 linkuse as main transcript	c.185+25T>G	intron_variant
FBLN1	NM_006485.4 linkuse as main transcript	c.185+25T>G	intron_variant
FBLN1	NM_006487.3 linkuse as main transcript	c.185+25T>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000327858.11 linkuse as main transcript	c.185+25T>G		intron_variant		1	NM_006486.3	P1	P23142-1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9630

AN:

152132

Hom.:

369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0410

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0766

Gnomad OTH

AF:

0.0502

GnomAD3 exomes

AF:

0.0572

AC:

11766

AN:

205682

Hom.:

410

AF XY:

0.0556

AC XY:

6132

AN XY:

110290

show subpopulations

Gnomad AFR exome

AF:

0.0502

Gnomad AMR exome

AF:

0.0303

Gnomad ASJ exome

AF:

0.0459

Gnomad EAS exome

AF:

0.00340

Gnomad SAS exome

AF:

0.0183

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.0546

GnomAD4 exome

AF:

0.0715

AC:

99885

AN:

1396086

Hom.:

3935

Cov.:

AF XY:

0.0696

AC XY:

48334

AN XY:

694202

show subpopulations

Gnomad4 AFR exome

AF:

0.0517

Gnomad4 AMR exome

AF:

0.0310

Gnomad4 ASJ exome

AF:

0.0445

Gnomad4 EAS exome

AF:

0.00297

Gnomad4 SAS exome

AF:

0.0180

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.0800

Gnomad4 OTH exome

AF:

0.0619

GnomAD4 genome

AF:

0.0633

AC:

9633

AN:

152250

Hom.:

369

Cov.:

AF XY:

0.0629

AC XY:

4682

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0529

Gnomad4 AMR

AF:

0.0410

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.00348

Gnomad4 SAS

AF:

0.0152

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.0767

Gnomad4 OTH

AF:

0.0497

Alfa

AF:

0.0651

Hom.:

Bravo

AF:

0.0581

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.11

DANN

Benign

0.44

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