Variant 22-45518795-T-C 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+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,597,416 control chromosomes in the GnomAD database, including 13,408 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4603 hom., cov: 32)

Exomes 𝑓: 0.093 ( 8805 hom. )

Consequence

FBLN1
NM_006486.3 splice_region, intron

Scores

Splicing: ADA: 0.00008021

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.213

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=-0.7).

BP6

Variant 22-45518795-T-C is Benign according to our data. Variant chr22-45518795-T-C is described in ClinVar as [Benign]. Clinvar id is 1286401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FBLN1	NM_006486.3 linkuse as main transcript	c.185+8T>C	splice_region_variant, intron_variant	ENST00000327858.11
FBLN1	NM_001996.4 linkuse as main transcript	c.185+8T>C	splice_region_variant, intron_variant
FBLN1	NM_006485.4 linkuse as main transcript	c.185+8T>C	splice_region_variant, intron_variant
FBLN1	NM_006487.3 linkuse as main transcript	c.185+8T>C	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000327858.11 linkuse as main transcript	c.185+8T>C		splice_region_variant, intron_variant		1	NM_006486.3	P1	P23142-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27925

AN:

152116

Hom.:

4583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.0882

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0845

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.0981

AC:

22276

AN:

226968

Hom.:

2053

AF XY:

0.0907

AC XY:

11095

AN XY:

122292

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.0521

Gnomad ASJ exome

AF:

0.0679

Gnomad EAS exome

AF:

0.0393

Gnomad SAS exome

AF:

0.0644

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.0838

Gnomad OTH exome

AF:

0.0770

GnomAD4 exome

AF:

0.0933

AC:

134869

AN:

1445182

Hom.:

8805

Cov.:

AF XY:

0.0908

AC XY:

65207

AN XY:

717998

show subpopulations

Gnomad4 AFR exome

AF:

0.452

Gnomad4 AMR exome

AF:

0.0562

Gnomad4 ASJ exome

AF:

0.0671

Gnomad4 EAS exome

AF:

0.0639

Gnomad4 SAS exome

AF:

0.0640

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.0869

Gnomad4 OTH exome

AF:

0.0996

GnomAD4 genome

AF:

0.184

AC:

28001

AN:

152234

Hom.:

4603

Cov.:

AF XY:

0.180

AC XY:

13382

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.0881

Gnomad4 ASJ

AF:

0.0718

Gnomad4 EAS

AF:

0.0510

Gnomad4 SAS

AF:

0.0671

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.0845

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.124

Hom.:

1097

Bravo

AF:

0.192

Asia WGS

AF:

0.100

AC:

347

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.1

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000080

dbscSNV1_RF

Benign

0.070

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