rs4596126

Positions:

• chr3-13618397-A-C

Variant summary

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

The NM_001004019.2(FBLN2):​c.1939+112A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 951,736 control chromosomes in the GnomAD database, including 44,859 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 0.39 (17009 hom., cov: 33)
  • Exomes 𝑓: 0.24 (27850 hom.)
• Consequence: FBLN2 NM_001004019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.93

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]

SNORA93 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN2	NM_001004019.2	c.1939+112A>C		intron_variant		ENST00000404922.8
SNORA93	NR_132775.1	n.17A>C		non_coding_transcript_exon_variant	1/1
FBLN2	NM_001165035.2	c.1939+112A>C		intron_variant
FBLN2	NM_001998.3	c.1939+112A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN2	ENST00000404922.8	c.1939+112A>C		intron_variant		5	NM_001004019.2	P1
FBLN2	ENST00000295760.11	c.1939+112A>C		intron_variant		1
FBLN2	ENST00000492059.5	c.1939+112A>C		intron_variant		2		P1
FBLN2	ENST00000477845.1	n.477+112A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59612 AN: 152092 Hom.: 16957 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.243 AC: 193914 AN: 799526 Hom.: 27850 AF XY: 0.242 AC XY: 98268 AN XY: 406698

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.392 AC: 59724 AN: 152210 Hom.: 17009 Cov.: 33 AF XY: 0.388 AC XY: 28843 AN XY: 74432

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.347

Alfa AF: 0.249 Hom.: 9609

Bravo AF: 0.411

Asia WGS AF: 0.303 AC: 1052 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	0.0040
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4596126; hg19: chr3-13659897;