rs17793957

Positions:

• chr3-13608420-C-G
• chr3-13608420-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004019.2(FBLN2):​c.1418+247C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,316 control chromosomes in the GnomAD database, including 387 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 0.059 (387 hom., cov: 33)
• Consequence: FBLN2 NM_001004019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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]

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 (NFE) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLN2	NM_001004019.2	c.1418+247C>G		intron_variant		ENST00000404922.8	NP_001004019.1
FBLN2	NM_001165035.2	c.1418+247C>G		intron_variant			NP_001158507.1
FBLN2	NM_001998.3	c.1418+247C>G		intron_variant			NP_001989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLN2	ENST00000404922.8	c.1418+247C>G		intron_variant		5	NM_001004019.2	ENSP00000384169	P1
FBLN2	ENST00000295760.11	c.1418+247C>G		intron_variant		1		ENSP00000295760
FBLN2	ENST00000492059.5	c.1418+247C>G		intron_variant		2		ENSP00000420042	P1

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8956 AN: 152198 Hom.: 386 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0589 AC: 8964 AN: 152316 Hom.: 387 Cov.: 33 AF XY: 0.0591 AC XY: 4402 AN XY: 74476

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0458 Hom.: 63

Bravo AF: 0.0508

Asia WGS AF: 0.0300 AC: 103 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	0.27
DANN	Benign	0.43

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: rs17793957; hg19: chr3-13649920;