22-45503078-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006486.3(FBLN1):c.79+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 1,231,462 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (2 hom.)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.388

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 22-45503078-G-C is Benign according to our data. Variant chr22-45503078-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3021231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN1	NM_006486.3	c.79+14G>C		intron_variant		ENST00000327858.11
FBLN1	NM_001996.4	c.79+14G>C		intron_variant
FBLN1	NM_006485.4	c.79+14G>C		intron_variant
FBLN1	NM_006487.3	c.79+14G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000327858.11	c.79+14G>C		intron_variant		1	NM_006486.3	P1

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 67 AN: 151916 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00924

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000554 AC: 2 AN: 3610 Hom.: 0 AF XY: 0.000428 AC XY: 1 AN XY: 2336

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00314

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000485 AC: 523 AN: 1079436 Hom.: 2 Cov.: 30 AF XY: 0.000505 AC XY: 259 AN XY: 512910

Gnomad4 AFR exome AF: 0.000223

Gnomad4 AMR exome AF: 0.000593

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000877

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.00100

GnomAD4 genome AF: 0.000441 AC: 67 AN: 152026 Hom.: 1 Cov.: 32 AF XY: 0.000431 AC XY: 32 AN XY: 74316

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.000655

Gnomad4 ASJ AF: 0.00924

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.000474

Bravo AF: 0.000601

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 17, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	7.6
Dann	Benign	0.83

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: rs545228163; hg19: chr22-45898958;