3-13601446-A-G

Variant names:

• chr3-13601446-A-G
• rs1878173
• NM_001004019.2:c.1307-6616A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004019.2(FBLN2):​c.1307-6616A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,012 control chromosomes in the GnomAD database, including 24,536 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 0.56 (24536 hom., cov: 32)
• Consequence: FBLN2 NM_001004019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 4 publications found

Genes affected

FBLN2 (HGNC:3601): (fibulin 2) This gene encodes an extracellular matrix protein, which belongs to the fibulin family. This protein binds various extracellular ligands and calcium. It may play a role during organ development, in particular, during the differentiation of heart, skeletal and neuronal structures. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FBLN2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• pulmonary arterial hypertension

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004019.2. 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
	FBLN2	NM_001004019.2	MANE Select	c.1307-6616A>G		intron	N/A	NP_001004019.1	P98095-2
	FBLN2	NM_001165035.2		c.1307-6616A>G		intron	N/A	NP_001158507.1	P98095-2
	FBLN2	NM_001998.3		c.1307-6616A>G		intron	N/A	NP_001989.2	P98095-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN2	ENST00000404922.8	TSL:5 MANE Select	c.1307-6616A>G		intron	N/A	ENSP00000384169.3	P98095-2
	FBLN2	ENST00000295760.11	TSL:1	c.1307-6616A>G		intron	N/A	ENSP00000295760.7	P98095-1
	FBLN2	ENST00000492059.5	TSL:2	c.1307-6616A>G		intron	N/A	ENSP00000420042.1	P98095-2

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85576 AN: 151894 Hom.: 24475 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.564 AC: 85699 AN: 152012 Hom.: 24536 Cov.: 32 AF XY: 0.561 AC XY: 41695 AN XY: 74284

African (AFR) AF: 0.651 AC: 27024 AN: 41482

American (AMR) AF: 0.500 AC: 7646 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3472

East Asian (EAS) AF: 0.649 AC: 3339 AN: 5148

South Asian (SAS) AF: 0.558 AC: 2684 AN: 4812

European-Finnish (FIN) AF: 0.504 AC: 5318 AN: 10560

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36047 AN: 67946

Other (OTH) AF: 0.553 AC: 1167 AN: 2110

Alfa AF: 0.542 Hom.: 88261

Bravo AF: 0.569

Asia WGS AF: 0.592 AC: 2061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.51
PhyloP100		0.27
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: rs1878173; hg19: chr3-13642946;