22-45502794-G-C

Position:

• chr22-45502794-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+454G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 164,764 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (213 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (2 hom.)
• Consequence: FBLN1 ENST00000411478.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62

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=-0.61).
• BP6: Variant 22-45502794-G-C is Benign according to our data. Variant chr22-45502794-G-C is described in ClinVar as [Benign]. Clinvar id is 1250203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 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+454G>C		intron_variant		4
FBLN1	ENST00000445110.5	c.-106+306G>C		intron_variant		4
FBLN1	ENST00000455233.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4950 AN: 151844 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0560

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.00482

Gnomad OTH AF: 0.0374

GnomAD4 exome AF: 0.00820 AC: 105 AN: 12812 Hom.: 2 Cov.: 1 AF XY: 0.00777 AC XY: 57 AN XY: 7338

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.0514

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00567

Gnomad4 OTH exome AF: 0.0207

GnomAD4 genome AF: 0.0326 AC: 4961 AN: 151952 Hom.: 213 Cov.: 32 AF XY: 0.0322 AC XY: 2390 AN XY: 74292

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.0560

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00482

Gnomad4 OTH AF: 0.0370

Alfa AF: 0.0292 Hom.: 14

Bravo AF: 0.0374

Asia WGS AF: 0.00842 AC: 29 AN: 3460

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	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.5
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs183195836; hg19: chr22-45898674;