22-45571646-G-A

Position:

• chr22-45571646-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.1698-2865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,106 control chromosomes in the GnomAD database, including 33,584 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 0.66 (33584 hom., cov: 32)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN1	NM_006486.3	c.1698-2865G>A		intron_variant		ENST00000327858.11	NP_006477.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN1	ENST00000327858.11	c.1698-2865G>A		intron_variant		1	NM_006486.3	ENSP00000331544.6

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100716 AN: 151988 Hom.: 33546 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.663 AC: 100800 AN: 152106 Hom.: 33584 Cov.: 32 AF XY: 0.661 AC XY: 49162 AN XY: 74342

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.652

Alfa AF: 0.640 Hom.: 66203

Bravo AF: 0.669

Asia WGS AF: 0.610 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.22

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: rs739215; hg19: chr22-45967526;