rs3773265

Variant names:

• chr3-13621579-G-A
• rs3773265
• NM_001004019.2:c.2156-196G>A

Variant summary

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

The NM_001004019.2(FBLN2):​c.2156-196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 152,194 control chromosomes in the GnomAD database, including 247 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 0.045 (247 hom., cov: 33)
• Consequence: FBLN2 NM_001004019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLN2	NM_001004019.2	c.2156-196G>A		intron_variant	Intron 8 of 17	ENST00000404922.8	NP_001004019.1
FBLN2	NM_001165035.2	c.2156-196G>A		intron_variant	Intron 8 of 17		NP_001158507.1
FBLN2	NM_001998.3	c.2155+1748G>A		intron_variant	Intron 8 of 16		NP_001989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8	c.2156-196G>A		intron_variant	Intron 8 of 17	5	NM_001004019.2	ENSP00000384169.3
FBLN2	ENST00000295760.11	c.2155+1748G>A		intron_variant	Intron 8 of 16	1		ENSP00000295760.7
FBLN2	ENST00000492059.5	c.2156-196G>A		intron_variant	Intron 8 of 17	2		ENSP00000420042.1

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6767 AN: 152076 Hom.: 244 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0445 AC: 6777 AN: 152194 Hom.: 247 Cov.: 33 AF XY: 0.0452 AC XY: 3366 AN XY: 74396

African (AFR) AF: 0.0119 AC: 496 AN: 41552

American (AMR) AF: 0.0744 AC: 1138 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3468

East Asian (EAS) AF: 0.162 AC: 835 AN: 5164

South Asian (SAS) AF: 0.0838 AC: 402 AN: 4800

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3295 AN: 67978

Other (OTH) AF: 0.0436 AC: 92 AN: 2110

Alfa AF: 0.0438 Hom.: 34

Bravo AF: 0.0454

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		0.22
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: rs3773265; hg19: chr3-13663079;