rs739215

Variant names:

• chr22-45571646-G-A
• rs739215
• NM_006486.3:c.1698-2865G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

FBLN1 Gene-Disease associations (from GenCC):

• FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• synpolydactyly type 2

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006486.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN1	NM_006486.3	MANE Select	c.1698-2865G>A		intron	N/A	NP_006477.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN1	ENST00000327858.11	TSL:1 MANE Select	c.1698-2865G>A		intron	N/A	ENSP00000331544.6	P23142-1
	FBLN1	ENST00000869160.1		c.1935-2865G>A		intron	N/A	ENSP00000539219.1
	FBLN1	ENST00000869154.1		c.1812-2865G>A		intron	N/A	ENSP00000539213.1

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

African (AFR) AF: 0.748 AC: 31045 AN: 41500

American (AMR) AF: 0.619 AC: 9461 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2166 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3375 AN: 5174

South Asian (SAS) AF: 0.652 AC: 3148 AN: 4830

European-Finnish (FIN) AF: 0.625 AC: 6604 AN: 10562

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42809 AN: 67966

Other (OTH) AF: 0.652 AC: 1379 AN: 2114

Alfa AF: 0.642 Hom.: 142848

Bravo AF: 0.669

Asia WGS AF: 0.610 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.22
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs739215; hg19: chr22-45967526;