rs743931

chr22-45563660-G-Achr22-45563660-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.1698-10851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,112 control chromosomes in the GnomAD database, including 41,923 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 0.74 (41923 hom., cov: 32)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN1	NM_006486.3	c.1698-10851G>A		intron_variant		ENST00000327858.11
FBLN1	NM_006485.4	c.1698-1224G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN1	ENST00000327858.11	c.1698-10851G>A		intron_variant		1	NM_006486.3	P1
FBLN1	ENST00000442170.6	c.1698-1224G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112608 AN: 151994 Hom.: 41891 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.741 AC: 112686 AN: 152112 Hom.: 41923 Cov.: 32 AF XY: 0.741 AC XY: 55132 AN XY: 74358

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.733

Alfa AF: 0.720 Hom.: 52073

Bravo AF: 0.740

Asia WGS AF: 0.642 AC: 2234 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	0.0030
Dann	Benign	0.54

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: rs743931; hg19: chr22-45959540;