22-45518581-G-A

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.80-101G>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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.781

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=-0.79).
• 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN1	NM_006486.3	c.80-101G>A		intron_variant		ENST00000327858.11
FBLN1	NM_001996.4	c.80-101G>A		intron_variant
FBLN1	NM_006485.4	c.80-101G>A		intron_variant
FBLN1	NM_006487.3	c.80-101G>A		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35661 AN: 151824 Hom.: 4492 Cov.: 31

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.: 9 AF XY: 0.250 AC XY: 94518 AN XY: 377682

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.: 31 AF XY: 0.233 AC XY: 17327 AN XY: 74280

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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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

Other links and lift over

dbSNP: rs7292978; hg19: chr22-45914461; COSMIC: COSV53048631; COSMIC: COSV53048631;