rs2051616

Positions:

• chr22-45567643-G-A

Variant summary

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

The NM_006486.3(FBLN1):​c.1698-6868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,818 control chromosomes in the GnomAD database, including 25,743 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 0.58 (25743 hom., cov: 31)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN1	NM_006486.3	c.1698-6868G>A		intron_variant		ENST00000327858.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000327858.11	c.1698-6868G>A		intron_variant		1	NM_006486.3	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88144 AN: 151700 Hom.: 25712 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.579

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.581 AC: 88216 AN: 151818 Hom.: 25743 Cov.: 31 AF XY: 0.580 AC XY: 43029 AN XY: 74162

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.580

Alfa AF: 0.569 Hom.: 19848

Bravo AF: 0.585

Asia WGS AF: 0.483 AC: 1682 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	0.95
DANN	Benign	0.48

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: rs2051616; hg19: chr22-45963523;