Variant chr22-45518581-G-A 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.80-101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 868,698 control chromosomes in the GnomAD database, including 29,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4494 hom., cov: 31)

Exomes 𝑓: 0.25 ( 24964 hom. )

Consequence

FBLN1
NM_006486.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.781

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=-0.79).

BP6

Variant 22-45518581-G-A is Benign according to our data. Variant chr22-45518581-G-A is described in ClinVar as [Benign]. Clinvar id is 1181351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FBLN1	NM_006486.3 linkuse as main transcript	c.80-101G>A	intron_variant	ENST00000327858.11
FBLN1	NM_001996.4 linkuse as main transcript	c.80-101G>A	intron_variant
FBLN1	NM_006485.4 linkuse as main transcript	c.80-101G>A	intron_variant
FBLN1	NM_006487.3 linkuse as main transcript	c.80-101G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000327858.11 linkuse as main transcript	c.80-101G>A		intron_variant		1	NM_006486.3	P1	P23142-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35661

AN:

151824

Hom.:

4492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.0533

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.254

AC:

181781

AN:

716756

Hom.:

24964

Cov.:

AF XY:

0.250

AC XY:

94518

AN XY:

377682

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.0405

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.235

AC:

35655

AN:

151942

Hom.:

4494

Cov.:

AF XY:

0.233

AC XY:

17327

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.0532

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.275

Hom.:

6376

Bravo

AF:

0.228

Asia WGS

AF:

0.100

AC:

351

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.3

DANN

Benign

0.41

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