chr22-45502712-G-C

Position:

• chr22-45502712-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000411478.5(FBLN1):​c.103+372G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 158,372 control chromosomes in the GnomAD database, including 32,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31128 hom., cov: 33)
  • Exomes 𝑓: 0.64 (1362 hom.)
• Consequence: FBLN1 ENST00000411478.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.33

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-45502712-G-C is Benign according to our data. Variant chr22-45502712-G-C is described in ClinVar as [Benign]. Clinvar id is 1235073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000411478.5	c.103+372G>C		intron_variant		4
FBLN1	ENST00000445110.5	c.-106+224G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96930 AN: 151648 Hom.: 31092 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.640 AC: 4230 AN: 6610 Hom.: 1362 AF XY: 0.651 AC XY: 2527 AN XY: 3882

Gnomad4 AFR exome AF: 0.636

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.629

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.639 AC: 97013 AN: 151762 Hom.: 31128 Cov.: 33 AF XY: 0.639 AC XY: 47420 AN XY: 74194

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.625

Alfa AF: 0.655 Hom.: 3021

Bravo AF: 0.647

Asia WGS AF: 0.538 AC: 1863 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9614486; hg19: chr22-45898592; COSMIC: COSV53053133;