22-45566024-G-T

Position:

• chr22-45566024-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006486.3(FBLN1):​c.1698-8487G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,738 control chromosomes in the GnomAD database, including 32,587 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (32449 hom., cov: 32)
  • Exomes 𝑓: 0.61 (138 hom.)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN1	NM_006486.3	c.1698-8487G>T		intron_variant		ENST00000327858.11	NP_006477.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN1	ENST00000327858.11	c.1698-8487G>T		intron_variant		1	NM_006486.3	ENSP00000331544.6

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99177 AN: 151928 Hom.: 32416 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.614 AC: 425 AN: 692 Hom.: 138 AF XY: 0.632 AC XY: 264 AN XY: 418

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.813

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.706

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.653 AC: 99258 AN: 152046 Hom.: 32449 Cov.: 32 AF XY: 0.652 AC XY: 48487 AN XY: 74322

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.649

Alfa AF: 0.747 Hom.: 7917

Bravo AF: 0.657

Asia WGS AF: 0.611 AC: 2125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.20

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: rs1985671; hg19: chr22-45961904;