22-45518661-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006486.3(FBLN1):c.80-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 1,575,144 control chromosomes in the GnomAD database, including 4,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (374 hom., cov: 32)
  • Exomes 𝑓: 0.072 (4083 hom.)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 22-45518661-C-T is Benign according to our data. Variant chr22-45518661-C-T is described in ClinVar as [Benign]. Clinvar id is 1260958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN1	NM_006486.3	c.80-21C>T		intron_variant		ENST00000327858.11
FBLN1	NM_001996.4	c.80-21C>T		intron_variant
FBLN1	NM_006485.4	c.80-21C>T		intron_variant
FBLN1	NM_006487.3	c.80-21C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000327858.11	c.80-21C>T		intron_variant		1	NM_006486.3	P1

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9769 AN: 152120 Hom.: 374 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0773

Gnomad OTH AF: 0.0516

GnomAD3 exomes AF: 0.0570 AC: 11320 AN: 198528 Hom.: 416 AF XY: 0.0559 AC XY: 5944 AN XY: 106388

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.0311

Gnomad ASJ exome AF: 0.0592

Gnomad EAS exome AF: 0.00219

Gnomad SAS exome AF: 0.0248

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.0747

Gnomad OTH exome AF: 0.0552

GnomAD4 exome AF: 0.0722 AC: 102674 AN: 1422906 Hom.: 4083 Cov.: 30 AF XY: 0.0706 AC XY: 49779 AN XY: 705218

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.0323

Gnomad4 ASJ exome AF: 0.0585

Gnomad4 EAS exome AF: 0.00212

Gnomad4 SAS exome AF: 0.0254

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.0796

Gnomad4 OTH exome AF: 0.0629

GnomAD4 genome AF: 0.0642 AC: 9773 AN: 152238 Hom.: 374 Cov.: 32 AF XY: 0.0637 AC XY: 4745 AN XY: 74440

Gnomad4 AFR AF: 0.0526

Gnomad4 AMR AF: 0.0432

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.00250

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0773

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0632 Hom.: 61

Bravo AF: 0.0590

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	13
Dann	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs76711905; hg19: chr22-45914541;